Showing papers in "Current Topics in Developmental Biology in 2015"
TL;DR: The principles and molecular mechanisms of the epithelial-mesenchymal interactions regulating successive stages of tooth formation are described, with special reference to the shift of tooth-forming potential from epithelium to mesenchyme.
Abstract: Reciprocal interactions between epithelial and mesenchymal tissues play a fundamental role in the morphogenesis of teeth and regulate all aspects of tooth development. Extensive studies on mouse tooth development over the past 25 years have uncovered the molecular details of the signaling networks mediating these interactions (reviewed by Jussila & Thesleff, 2012; Lan, Jia, & Jiang, 2014). Five conserved signaling pathways, namely, the Wnt, BMP, FGF, Shh, and Eda, are involved in the mediation of the successive reciprocal epithelial-mesenchymal cross talk which follows the general principle of morphogenetic interactions (Davidson, 1993). The pathways regulate the expression of transcription factors which confer the identity of dental epithelium and mesenchyme. The signals and transcription factors are integrated in complex signaling networks whose fine-tuning allows the generation of the variation in tooth morphologies. In this review, we describe the principles and molecular mechanisms of the epithelial-mesenchymal interactions regulating successive stages of tooth formation: (i) the initiation of tooth development, with special reference to the shift of tooth-forming potential from epithelium to mesenchyme; (ii) the morphogenesis of the tooth crown, focusing on the roles of epithelial signaling centers; (iii) the differentiation of odontoblasts and ameloblasts, which produce dentin and enamel, respectively; and (iv) the maintenance of dental stem cells, which support the continuous growth of teeth.
214 citations
TL;DR: A detailed anatomy of the zebrafish cranio-facial skeleton is described in this article, along with its applications as models for the mammalian jaw, middle ear, palate, and cranial sutures.
Abstract: The formation of the face and skull involves a complex series of developmental events mediated by cells derived from the neural crest, endoderm, mesoderm, and ectoderm. Although vertebrates boast an enormous diversity of adult facial morphologies, the fundamental signaling pathways and cellular events that sculpt the nascent craniofacial skeleton in the embryo have proven to be highly conserved from fish to man. The zebrafish Danio rerio, a small freshwater cyprinid fish from eastern India, has served as a popular model of craniofacial development since the 1990s. Unique strengths of the zebrafish model include a simplified skeleton during larval stages, access to rapidly developing embryos for live imaging, and amenability to transgenesis and complex genetics. In this chapter, we describe the anatomy of the zebrafish craniofacial skeleton; its applications as models for the mammalian jaw, middle ear, palate, and cranial sutures; the superior imaging technology available in fish that has provided unprecedented insights into the dynamics of facial morphogenesis; the use of the zebrafish to decipher the genetic underpinnings of craniofacial biology; and finally a glimpse into the most promising future applications of zebrafish craniofacial research.
122 citations
TL;DR: In this state, similarly to activated keratinocytes during re-epithelialization, cells can initiate a cohort migration and engage into a transient and reversible EMT controlled by the local environment prior to efficient intravasation and metastasis.
Abstract: Epithelial-mesenchymal transition (EMT) is a developmental cellular process occurring during early embryo development, including gastrulation and neural crest cell migration. It can be broken down in distinct functional steps: (1) loss of baso-apical polarization characterized by cytoskeleton, tight junctions, and hemidesmosomes remodeling; (2) individualization of cells, including a decrease in cell-cell adhesion forces, (3) emergence of motility, and (4) invasive properties, including passing through the subepithelial basement membrane. These phases occur in an uninterrupted process, without requiring mitosis, in an order and with a degree of completion dictated by the microenvironment. The whole process reflects the activation of specific transcription factor families, called EMT transcription factors. Several mechanisms can combine to induce EMT. Some are reversible, involving growth factors and cytokines and/or environmental signals including extracellular matrix and local physical conditions. Others are irreversible, such as genomic alterations during carcinoma progression, along a selective and irreversible clonal drift. In carcinomas, these signals can converge to initiate a metastable phenotype. In this state, similarly to activated keratinocytes during re-epithelialization, cells can initiate a cohort migration and engage into a transient and reversible EMT controlled by the local environment prior to efficient intravasation and metastasis. EMT transcription factors also participate in cancer progression by inducing apoptosis resistance and maintaining stem-like properties exposed in tumor recurrences. These properties, very important on a clinical point of view, are not intrinsically linked to EMT, but can share common pathways.
120 citations
TL;DR: What is known about autophagy, its regulation, its role both in cell life and cell death, and what is knownAbout autophagic cell death in vivo are reviewed.
Abstract: Macroautophagy (hereafter referred to as autophagy) is a process used by the cell to deliver cytoplasmic components to the lysosome for degradation. Autophagy is most often associated with cell survival, as it provides cells with molecular building blocks during periods of nutrient deprivation and also aids in the elimination of damaged organelles and protein aggregates. However, autophagy has also been implicated in cell death. Here, we review what is known about autophagy, its regulation, its role both in cell life and cell death, and what is known about autophagic cell death in vivo.
119 citations
TL;DR: In mouse, the oocyte-to-embryo transition entails converting a highly differentiated oocyte to totipotent blastomeres, driven by degradation of maternal mRNAs, which results in loss of oocyte identity, and reprogramming of gene expression during the course of zygotic gene activation, which occurs primarily during the two-cell stage and confers blastomere totipotency.
Abstract: In mouse, the oocyte-to-embryo transition entails converting a highly differentiated oocyte to totipotent blastomeres. This transition is driven by degradation of maternal mRNAs, which results in loss of oocyte identity, and reprogramming of gene expression during the course of zygotic gene activation, which occurs primarily during the two-cell stage and confers blastomere totipotency. Full-grown oocytes are transcriptionally quiescent and mRNAs are remarkably stable in oocytes due to the RNA-binding protein MSY2, which stabilizes mRNAs, and low activity of the 5' and 3' RNA degradation machinery. Oocyte maturation initiates a transition from mRNA stability to instability due to phosphorylation of MSY2, which makes mRNAs more susceptible to the RNA degradation machinery, and recruitment of dormant maternal mRNAs that encode for critical components of the 5' and 3' RNA degradation machinery. Small RNAs (miRNA, siRNA, and piRNA) play little, if any, role in mRNA degradation that occurs during maturation. Many mRNAs are totally degraded but a substantial fraction is only partially degraded, their degradation completed by the end of the two-cell stage. Genome activation initiates during the one-cell stage, is promiscuous, low level, and genome wide (and includes both inter- and intragenic regions) and produces transcripts that are inefficiently spliced and polyadenylated. The major wave of genome activation in two-cell embryos involves expression of thousands of new genes. This unique pattern of gene expression is the product of maternal mRNAs recruited during maturation that encode for transcription factors and chromatin remodelers, as well as dramatic changes in chromatin structure due to incorporation of histone variants and modified histones.
116 citations
TL;DR: The molecular networks controlling both mandible and tongue development are reviewed in detail and their mechanical relationship and evolution are discussed as well as the potential for stem cell-based therapies for disorders affecting these organs.
Abstract: The tongue and mandible have common origins. They arise simultaneously from the mandibular arch and are coordinated in their development and growth, which is evident from several clinical conditions such as Pierre Robin sequence. Here, we review in detail the molecular networks controlling both mandible and tongue development. We also discuss their mechanical relationship and evolution as well as the potential for stem cell-based therapies for disorders affecting these organs.
110 citations
TL;DR: Recent advances in research on nectins and Necls/Cadms are summarized, which shows that these cell adhesion molecules are crucial for both physiology and pathology.
Abstract: Nectins and nectin-like molecules (Necls)/Cadms are Ca(2+)-independent immunoglobulin superfamily cell adhesion molecules, expressed in most cell types. Nectins mediate not only homotypic but also heterotypic cell-cell adhesion, in contrast to classic cadherins which participate only in homophilic adhesion. Nectins and Necls function in organogenesis of the eye, inner ear, tooth, and cerebral cortex and in a variety of developmental processes including spermatogenesis, axon guidance, synapse formation, and myelination. They are also involved in various diseases, such as viral infection, hereditary ectodermal dysplasia, Alzheimer's disease, autism spectrum disorder, and cancer. Thus, nectins and Necls are crucial for both physiology and pathology. This review summarizes recent advances in research on these cell adhesion molecules in development and pathogenesis.
104 citations
TL;DR: An overview of molecular mechanisms driving maternal mRNA clearance during the maternal-to-zygotic transition (MZT) is provided in this article, where the developmental consequences of losing components of this gene regulation are discussed.
Abstract: Cellular transitions occur at all stages of organismal life from conception to adult regeneration. Changing cellular state involves three main features: activating gene expression necessary to install the new cellular state, modifying the chromatin status to stabilize the new gene expression program, and removing existing gene products to clear out the previous cellular program. The maternal-to-zygotic transition (MZT) is one of the most profound changes in the life of an organism. It involves gene expression remodeling at all levels, including the active clearance of the maternal oocyte program to adopt the embryonic totipotency. In this chapter, we provide an overview of molecular mechanisms driving maternal mRNA clearance during the MZT, describe the developmental consequences of losing components of this gene regulation, and illustrate how remodeling of gene expression during the MZT is common to other cellular transitions with parallels to cellular reprogramming.
101 citations
TL;DR: This review will summarize major recent advances and discuss major remaining gaps in the understanding of cellular and molecular mechanisms controlling palatogenesis.
Abstract: Palatogenesis involves the initiation, growth, morphogenesis, and fusion of the primary and secondary palatal shelves from initially separate facial prominences during embryogenesis to form the intact palate separating the oral cavity from the nostrils. The palatal shelves consist mainly of cranial neural crest-derived mesenchymal cells covered by a simple embryonic epithelium. The growth and patterning of the palatal shelves are controlled by reciprocal epithelial-mesenchymal interactions regulated by multiple signaling pathways and transcription factors. During palatal shelf outgrowth, the embryonic epithelium develops a "teflon" coat consisting of a single, continuous layer of periderm cells that prevents the facial prominences and palatal shelves from forming aberrant interepithelial adhesions. Palatal fusion involves not only spatiotemporally regulated disruption of the periderm but also dynamic cellular and molecular processes that result in adhesion and intercalation of the palatal medial edge epithelia to form an intershelf epithelial seam, and subsequent dissolution of the epithelial seam to form the intact roof of the oral cavity. The complexity of regulation of these morphogenetic processes is reflected by the common occurrence of cleft palate in humans. This review will summarize major recent advances and discuss major remaining gaps in the understanding of cellular and molecular mechanisms controlling palatogenesis.
88 citations
TL;DR: Advances in inducible gene expression and knockdown, CRISPR/Cas9 technology, and fluorescent labeling of genetically modified cells offer the opportunity to test the roles of diverse adhesion systems and to develop a mechanistic understanding of how cell adhesion regulates development and cancer.
Abstract: Epithelial tissues are essential for barrier function, secretion, and regulation of fluid transport. Their function requires cell polarity and cell-cell adhesion, mediated through intercellular junctions. Conversely, disruption of adhesion and polarity is thought to drive cancer progression. The mammary gland is an important model for cell adhesion due to its postnatal hormonally regulated development; ducts undergo branching morphogenesis in response to steroid hormones during puberty. These hormonal signals induce a transition from simple to stratified architecture, initiated by asymmetric luminal cell divisions. Ductal elongation is accomplished by this multilayered, low-polarity epithelium, and polarity is reestablished as elongation ceases. The requirement for cell adhesion has been tested in 3D culture and in vivo, using gene deletion, knockdown, and misexpression in both developmental and homeostatic contexts. Attention has focused on E-cadherin, the major classical cadherin in luminal epithelial cells. Classic studies revealed a requirement for E-cadherin during lactation, and E-cadherin loss is widely posited to promote metastasis. However, recent findings demonstrated a broader requirement for E-cadherin during branching morphogenesis and homeostasis and also, surprisingly, in epithelial dissemination. These studies suggest that long-standing models of the role of adhesion in epithelial biology need to be revisited. Advances in inducible gene expression and knockdown, CRISPR/Cas9 technology, and fluorescent labeling of genetically modified cells offer the opportunity to test the roles of diverse adhesion systems and to develop a mechanistic understanding of how cell adhesion regulates development and cancer.
87 citations
TL;DR: In addition to individual adhesive functions, emerging ideas on mechanosensation/transduction of junctions in the epidermis, noncanonical roles for adhesion proteins, and crosstalk/interdependencies between the junctional systems are discussed.
Abstract: Cell–cell adhesions are necessary for structural integrity and barrier formation of the epidermis. Here, we discuss insights from genetic and cell biological studies into the roles of individual cell–cell junctions and their composite proteins in regulating epidermal development and function. In addition to individual adhesive functions, we will discuss emerging ideas on mechanosensation/transduction of junctions in the epidermis, noncanonical roles for adhesion proteins, and crosstalk/interdependencies between the junctional systems. These studies have revealed that cell adhesion proteins are connected to many aspects of tissue physiology including growth control, differentiation, and inflammation.
TL;DR: The intimate relationship between the clearance of maternal gene products and the activation of the embryo's own genome is highlighted, and the fact that each of these complementary components of the maternal-to-zygotic transition can be subdivided into several phases that serve different biological roles and are regulated by distinct factors are discussed.
Abstract: Drosophila late-stage oocytes and early embryos are transcriptionally silent. Thus, control of gene expression during these developmental periods is posttranscriptional and posttranslational. Global changes in the transcriptome and proteome occur during oocyte maturation, after egg activation and fertilization, and upon zygotic genome activation. We review the scale, content, and dynamics of these global changes; the factors that regulate these changes; and the mechanisms by which they are accomplished. We highlight the intimate relationship between the clearance of maternal gene products and the activation of the embryo's own genome, and discuss the fact that each of these complementary components of the maternal-to-zygotic transition can be subdivided into several phases that serve different biological roles and are regulated by distinct factors.
TL;DR: The results show that, first, the brain is a structural platform that influences positioning of the facial primordia, and brain growth influences the timing ofPrimordia fusion.
Abstract: Morphogenesis of the brain and face is intrinsically linked by a number of factors. These include: origins of tissues, adjacency allowing their physical interactions, and molecular cross talk controlling growth. Neural crest cells that form the facial primordia originate on the dorsal neural tube. In the caudal pharyngeal arches, a Homeobox code regulates arch identity. In anterior regions, positional information is acquired locally. Second, the brain is a structural platform that influences positioning of the facial primordia, and brain growth influences the timing of primordia fusion. Third, the brain helps induce a signaling center, the frontonasal ectodermal zone, in the ectoderm, which participates in patterned growth of the upper jaw. Similarly, signals from neural crest cells regulate expression of fibroblast growth factor 8 in the anterior neural ridge, which controls growth of the anterior forebrain. Disruptions to these interactions have significant consequences for normal development of the craniofacial complex, leading to structural malformations and birth defects.
TL;DR: This review highlights new findings in the field of taste development, including how taste buds are patterned and how taste cell fate is regulated, and discusses whether a specialized taste bud stem cell population exists and how extrinsic signals can define which cell lineages are generated.
Abstract: Taste is one of the fundamental senses, and it is essential for our ability to ingest nutritious substances and to detect and avoid potentially toxic ones. Taste buds, which are clusters of neuroepithelial receptor cells, are housed in highly organized structures called taste papillae in the oral cavity. Whereas the overall structure of the taste periphery is conserved in almost all vertebrates examined to date, the anatomical, histological, and cell biological, as well as potentially the molecular details of taste buds in the oral cavity are diverse across species and even among individuals. In mammals, several types of gustatory papillae reside on the tongue in highly ordered arrangements, and the patterning and distribution of the mature papillae depend on coordinated molecular events in embryogenesis. In this review, we highlight new findings in the field of taste development, including how taste buds are patterned and how taste cell fate is regulated. We discuss whether a specialized taste bud stem cell population exists and how extrinsic signals can define which cell lineages are generated. We also address the question of whether molecular regulation of taste cell renewal is analogous to that of taste bud development. Finally, we conclude with suggestions for future directions, including the potential influence of the maternal diet and maternal health on the sense of taste in utero.
TL;DR: The transcriptional and signaling factors that regulate key steps of placode development, influence subsequent sensory neuron specification, and discuss what is known about mutations in some of the essential PPE genes that underlie human congenital syndromes are summarized.
Abstract: Cranial sensory placodes derive from discrete patches of the head ectoderm and give rise to numerous sensory structures. During gastrulation, a specialized "neural border zone" forms around the neural plate in response to interactions between the neural and nonneural ectoderm and signals from adjacent mesodermal and/or endodermal tissues. This zone subsequently gives rise to two distinct precursor populations of the peripheral nervous system: the neural crest and the preplacodal ectoderm (PPE). The PPE is a common field from which all cranial sensory placodes arise (adenohypophyseal, olfactory, lens, trigeminal, epibranchial, otic). Members of the Six family of transcription factors are major regulators of PPE specification, in partnership with cofactor proteins such as Eya. Six gene activity also maintains tissue boundaries between the PPE, neural crest, and epidermis by repressing genes that specify the fates of those adjacent ectodermally derived domains. As the embryo acquires anterior-posterior identity, the PPE becomes transcriptionally regionalized, and it subsequently becomes subdivided into specific placodes with distinct developmental fates in response to signaling from adjacent tissues. Each placode is characterized by a unique transcriptional program that leads to the differentiation of highly specialized cells, such as neurosecretory cells, sensory receptor cells, chemosensory neurons, peripheral glia, and supporting cells. In this review, we summarize the transcriptional and signaling factors that regulate key steps of placode development, influence subsequent sensory neuron specification, and discuss what is known about mutations in some of the essential PPE genes that underlie human congenital syndromes.
TL;DR: This review focuses on signals that originate from the larger family of cadherins that are inwardly directed to the nucleus, and thus have roles in gene control or nuclear structure-function, and on cadherin complexes that operate as stoichiometric competitors of nuclear signals.
Abstract: The arrival of multicellularity in evolution facilitated cell–cell signaling in conjunction with adhesion. As the ectodomains of cadherins interact with each other directly in trans (as well as in cis), spanning the plasma membrane and associating with multiple other entities, cadherins enable the transduction of “outside-in” or “inside-out” signals. We focus this review on signals that originate from the larger family of cadherins that are inwardly directed to the nucleus, and thus have roles in gene control or nuclear structure–function. The nature of cadherin complexes varies considerably depending on the type of cadherin and its context, and we will address some of these variables for classical cadherins versus other family members. Substantial but still fragmentary progress has been made in understanding the signaling mediators used by varied cadherin complexes to coordinate the state of cell–cell adhesion with gene expression. Evidence that cadherin intracellular binding partners also localize to the nucleus is a major point of interest. In some models, catenins show reduced binding to cadherin cytoplasmic tails favoring their engagement in gene control. When bound, cadherins may serve as stoichiometric competitors of nuclear signals. Cadherins also directly or indirectly affect numerous signaling pathways (e.g., Wnt, receptor tyrosine kinase, Hippo, NFκB, and JAK/STAT), enabling cell–cell contacts to touch upon multiple biological outcomes in embryonic development and tissue homeostasis.
TL;DR: Analysis of the pathophysiology underling craniosynostosis has identified a variety of cellular mechanisms, mediated by a range of signaling pathways and effector transcription factors, including loss of boundary integrity, altered sutural cell specification in embryos, and loss of a suture stem cell population in adults.
Abstract: The skull vault is a complex, exquisitely patterned structure that plays a variety of key roles in vertebrate life, ranging from the acquisition of food to the support of the sense organs for hearing, smell, sight, and taste. During its development, it must meet the dual challenges of protecting the brain and accommodating its growth. The bones and sutures of the skull vault are derived from cranial neural crest and head mesoderm. The frontal and parietal bones develop from osteogenic rudiments in the supraorbital ridge. The coronal suture develops from a group of Shh-responsive cells in the head mesoderm that are collocated, with the osteogenic precursors, in the supraorbital ridge. The osteogenic rudiments and the prospective coronal suture expand apically by cell migration. A number of congenital disorders affect the skull vault. Prominent among these is craniosynostosis, the fusion of the bones at the sutures. Analysis of the pathophysiology underling craniosynostosis has identified a variety of cellular mechanisms, mediated by a range of signaling pathways and effector transcription factors. These cellular mechanisms include loss of boundary integrity, altered sutural cell specification in embryos, and loss of a suture stem cell population in adults. Future work making use of genome-wide transcriptomic approaches will address the deep structure of regulatory interactions and cellular processes that unify these seemingly diverse mechanisms.
TL;DR: The current understanding of how the cell cycle is remodeled over the course of the Drosophila MZT is discussed, and how the temporal precision of this event is linked to contemporaneous alterations in genome-wide chromatin structure and transcriptional activity.
Abstract: During the maternal-to-zygotic transition (MZT), major changes in cell cycle regulation coincide with large-scale zygotic genome activation. In this chapter, we discuss the current understanding of how the cell cycle is remodeled over the course of the Drosophila MZT, and how the temporal precision of this event is linked to contemporaneous alterations in genome-wide chromatin structure and transcriptional activity. The cell cycle is initially lengthened during the MZT by activation of the DNA replication checkpoint but, subsequently, zygotically supplied factors are essential for establishing lasting modifications to the cell cycle.
TL;DR: The current understanding of the processes that mediate the reprogramming of the early embryonic genome and facilitate transcriptional activation during the early stages of Drosophila development are reviewed.
Abstract: During the first stages of metazoan development, the genomes of the highly specified sperm and egg must unite and be reprogrammed to allow for the generation of a new organism. This process is controlled by maternally deposited products. Initially, the zygotic genome is largely transcriptionally quiescent, and it is not until hours later that the zygotic genome takes control of development. The transcriptional activation of the zygotic genome is tightly coordinated with the degradation of the maternal products. Here, we review the current understanding of the processes that mediate the reprogramming of the early embryonic genome and facilitate transcriptional activation during the early stages of Drosophila development.
TL;DR: The development of coronary vessels occurs through an epithelial-to-mesenchymal transformation of proepicardial cells, followed by vasculogenesis in the subepicocardial layer, assembly and remodeling of a primitive coronary plexus, and recruitment of a smooth-muscle coating as mentioned in this paper.
Abstract: Publisher Summary This chapter discusses the development in coronary vessels Formation of the coronary vessels occurs through an epithelial-to-mesenchymal transformation of proepicardial cells, followed by vasculogenesis in the subepicardial layer, assembly and remodeling of a primitive coronary plexus, and recruitment of a smooth-muscle coating This chapter reviews the current understanding of the origins and development of the coronary vasculature, with an emphasis on formation of coronary smooth muscle Progenitors for the coronary vasculature are found in the proepicardium Proepicardial cells arise independently of the heart itself and provide epicardial cells to the outer surface of the looped heart tube during cardiac development Fate-mapping studies show that proepicardial cells are forerunners for the endothelium and smooth muscle of the coronary vasculature, and the connective tissue cells that form the coronary adventitia and interstitial matrix of the myocardium
TL;DR: The capacity for the kidney to form via self-organization has now been established both via the recapitulation of expected morphogenetic interactions after complete dissociation and reassociation of cellular components during development as well as the in vitro formation of 3D kidney organoids from human pluripotent stem cells.
Abstract: The mammalian kidney forms via cell-cell interactions between an epithelial outgrowth of the nephric duct and the surrounding nephrogenic mesenchyme. Initial morphogenetic events include ureteric bud branching to form the collecting duct (CD) tree and mesenchymal-to-epithelial transitions to form the nephrons, requiring reciprocal induction between adjacent mesenchyme and epithelial cells. Within the tips of the branching ureteric epithelium, cells respond to mesenchyme-derived trophic factors by proliferation, migration, and mitosis-associated cell dispersal. Self-inhibition signals from one tip to another play a role in branch patterning. The position, survival, and fate of the nephrogenic mesenchyme are regulated by ECM and secreted signals from adjacent tip and stroma. Signals from the ureteric tip promote mesenchyme self-renewal and trigger nephron formation. Subsequent fusion to the CDs, nephron segmentation and maturation, and formation of a patent glomerular basement membrane also require specialized cell-cell interactions. Differential cadherin, laminin, nectin, and integrin expression, as well as intracellular kinesin and actin-mediated regulation of cell shape and adhesion, underlies these cell-cell interactions. Indeed, the capacity for the kidney to form via self-organization has now been established both via the recapitulation of expected morphogenetic interactions after complete dissociation and reassociation of cellular components during development as well as the in vitro formation of 3D kidney organoids from human pluripotent stem cells. As we understand more about how the many cell-cell interactions required for kidney formation operate, this enables the prospect of bioengineering replacement structures based on these self-organizing properties.
TL;DR: The basic biology of dental stem cells, their functions, and potential clinical uses are described and much is being learnt about the general properties of these stem cells for the incisor as a model system.
Abstract: Human teeth contain stem cells in all their mesenchymal-derived tissues, which include the pulp, periodontal ligament, and developing roots, in addition to the support tissues such as the alveolar bone. The precise roles of these cells remain poorly understood and most likely involve tissue repair mechanisms but their relative ease of harvesting makes teeth a valuable potential source of mesenchymal stem cells (MSCs) for therapeutic use. These dental MSC populations all appear to have the same developmental origins, being derived from cranial neural crest cells, a population of embryonic stem cells with multipotential properties. In rodents, the incisor teeth grow continuously throughout life, a feature that requires populations of continuously active mesenchymal and epithelial stem cells. The discrete locations of these stem cells in the incisor have rendered them amenable for study and much is being learnt about the general properties of these stem cells for the incisor as a model system. The incisor MSCs appear to be a heterogeneous population consisting of cells from different neural crest-derived tissues. The epithelial stem cells can be traced directly back in development to a Sox10(+) population present at the time of tooth initiation. In this review, we describe the basic biology of dental stem cells, their functions, and potential clinical uses.
TL;DR: This chapter reviews the methods and theory that enable the application of modern landmark-based morphometrics to developmental biology and craniofacial development, in particular and discusses the principal statistical methods for quantifying and comparing morphological variation and covariation structure within and among groups.
Abstract: Recent studies have shown how volumetric imaging and morphometrics can add significantly to our understanding of morphogenesis, the developmental basis for variation, and the etiology of structural birth defects. On the other hand, the complex questions and diverse imaging data in developmental biology present morphometrics with more complex challenges than applications in virtually any other field. Meeting these challenges is necessary in order to understand the mechanistic basis for variation in complex morphologies. This chapter reviews the methods and theory that enable the application of modern landmark-based morphometrics to developmental biology and craniofacial development, in particular. We discuss the theoretical foundations of morphometrics as applied to development and review the basic approaches to the quantification of morphology. Focusing on geometric morphometrics, we discuss the principal statistical methods for quantifying and comparing morphological variation and covariation structure within and among groups. Finally, we discuss the future directions for morphometrics in developmental biology that will be required for approaches that enable quantitative integration across the genotype-phenotype map.
TL;DR: Current understanding of cardiac NCC-mediated vascular remodeling and signaling pathways important for this process are reviewed and their contribution to the cardiac valves as well as the still contentious role of cardiacNCCs in the development of the myocardium and conductive system of the heart are discussed.
Abstract: Cardiac neural crest cells (NCCs) are a transient, migratory cell population exclusive to vertebrate embryos. Ablation, transplantation, and lineage-tracing experiments in chick and mouse have demonstrated their essential role in the remodeling of the initially bilateral and symmetric pharyngeal artery pairs into an aortic arch and for the septation of the cardiac outflow tract into the base of the pulmonary artery and aorta. Accordingly, defective cardiac NCC function is a common cause of congenital birth defects. Here, we review our current understanding of cardiac NCC-mediated vascular remodeling and signaling pathways important for this process. We additionally discuss their contribution to the cardiac valves as well as the still contentious role of cardiac NCCs in the development of the myocardium and conductive system of the heart.
TL;DR: In this organism, apoptosis as a fate is conferred by the transcriptional induction of the IAP-antagonists, and posttranscriptional mechanisms are employed to eliminate damaged or virus-infected cells, limit neuroblast numbers, generate neuronal diversity, and sculpt tissue morphogenesis.
Abstract: Inhibitors of apoptosis (IAPs) family of genes encode baculovirus IAP-repeat domain-containing proteins with antiapoptotic function. These proteins also contain RING or UBC domains and act by binding to major proapoptotic factors and ubiquitylating them. High levels of IAPs inhibit caspase-mediated apoptosis. For these cells to undergo apoptosis, IAP function must be neutralized by IAP-antagonists. Mammalian IAP knockouts do not exhibit obvious developmental phenotypes, but the cells are more sensitized to apoptosis in response to injury. Loss of the mammalian IAP-antagonist ARTS results in reduced stem cell apoptosis. In addition to the antiapoptotic properties, IAPs regulate the innate immune response, and the loss of IAP function in humans is associated with immunodeficiency. The roles of IAPs in Drosophila apoptosis regulation are more apparent, where the loss of IAP1, or the expression of IAP-antagonists in Drosophila cells, is sufficient to trigger apoptosis. In this organism, apoptosis as a fate is conferred by the transcriptional induction of the IAP-antagonists. Many signaling pathways often converge on shared enhancer regions of IAP-antagonists. Cell death sensitivity is further regulated by posttranscriptional mechanisms, including those regulated by kinases, miRs, and ubiquitin ligases. These mechanisms are employed to eliminate damaged or virus-infected cells, limit neuroblast (neural stem cell) numbers, generate neuronal diversity, and sculpt tissue morphogenesis.
TL;DR: Some of the most intriguing signals produced by apoptotic cells during the course of normal development as well as during physiological disturbances such as atherosclerosis and cancer are highlighted.
Abstract: Apoptosis is a carefully choreographed process of cellular self-destruction in the absence of inflammation. During the death process, apoptotic cells actively communicate with their environment, signaling to both their immediate neighbors as well as distant sentinels. Some of these signals direct the anti-inflammatory immune response, instructing specific subsets of phagocytes to participate in the limited and careful clearance of dying cellular debris. These immunomodulatory signals can also regulate the activation state of the engulfing phagocytes. Other signals derived from apoptotic cells contribute to tissue growth control with the common goal of maintaining tissue integrity. Derangements in these growth control signals during prolonged apoptosis can lead to excessive cell loss or proliferation. Here, we highlight some of the most intriguing signals produced by apoptotic cells during the course of normal development as well as during physiological disturbances such as atherosclerosis and cancer.
TL;DR: Focusing on epithelia, it is argued that E-cadherin junctions can be considered as active mechanical agents, which contribute to the assembly of actomyosin at the junctional cortex itself.
Abstract: In this chapter, we discuss the cell biology of contractility at cell–cell junctions. As discussed elsewhere in this volume, contractile forces play key roles in development and tissue homeostasis. Here, we review our understanding of the cellular mechanisms that functionally and physically link cadherin adhesion to the actomyosin contractile apparatus of the cell. Focusing on epithelia, we argue that E-cadherin junctions can be considered as active mechanical agents, which contribute to the assembly of actomyosin at the junctional cortex itself. This reflects cortical signaling, notably that regulated by the Rho GTPase, coordinated with actin regulation at junctions. The product, contractile tension at junctions, can then be regarded as an emergent property of a complex dynamical system that integrates adhesion with the cytoskeleton.
TL;DR: In this article, the authors describe key studies that highlight VE-cadherin as a regulatory hub in endothelial cell signaling during angiogenesis, vessel morphogenesis, and vascular development.
Abstract: Blood and lymphatic vessels make up the vascular system of vertebrates and are lined by specialized endothelial cells. The connections between endothelial cells are formed by adhesion molecules and are essential to maintain cell-cell adhesion, cell-cell communication, and the integrity of our vascular tubes. One key adhesion molecule is the adherens junctional protein vascular endothelial cadherin (VE-cadherin). In addition to its role in endothelial adhesion, it is emerging that this protein is actively involved in modulating key cellular signaling cascades within endothelial cells and can control the behavior of endothelial cells during development and morphogenesis. We describe key studies that highlight VE-cadherin as a regulatory hub in endothelial cell signaling during angiogenesis, vessel morphogenesis, and vascular development.
TL;DR: Current knowledge is summarized, based mainly on the in vivo study of morphogenesis in the fruit fly Drosophila melanogaster, that the contractile machinery responsible for cell shape changes, actomyosin, can in fact be organized into a number of different functional assemblies.
Abstract: During embryonic development, cells become organized into complex tissues. Cells need to adhere and communicate with their immediate and remote neighbors to allow morphogenesis to take place in a coordinated way. Cell-cell adhesion, mediated by transmembrane adhesion receptors such as Cadherins and their intracellular interaction partners, is intimately linked to cell contractility that drives cell shape changes. Research in recent years has revealed that the contractile machinery responsible for cell shape changes, actomyosin, can in fact be organized into a number of different functional assemblies such as cortical-junctional actomyosin, apical-medial actomyosin, supracellular actomyosin cables as well as basal actomyosin networks. During coordinated shape changes of a tissue, these assemblies have to be functionally and mechanically linked between cells through cell-cell junctions. Although many actin-binding proteins associated with adherens junctions have been identified, which specific factors are required for the linkage of particular actomyosin assemblies to junctions is not well understood. This review will summarize our current knowledge, based mainly on the in vivo study of morphogenesis in the fruit fly Drosophila melanogaster.
TL;DR: In Caenorhabditis elegans, posttranslational and posttranscriptional regulation of the maternal proteins and mRNAs that are loaded into the developing oocytes is sufficient to direct development prior to gastrulation.
Abstract: In Caenorhabditis elegans, the first zygotic transcription can be detected in the 4-cell stage C. elegans embryo, a little over 2h after fertilization. However, early development until the onset of gastrulation at approximately the 28-cell stage takes place normally even in the absence of zygotic transcription. Therefore, posttranslational and posttranscriptional regulation of the maternal proteins and mRNAs, respectively, that are loaded into the developing oocytes is sufficient to direct development prior to gastrulation. Protein phosphorylation is extensively used throughout the C. elegans maternal-to-zygotic transition (MZT): (1) for maternal protein activation, (2) for coordination of the meiotic and mitotic cell cycle, (3) to mark specific proteins for degradation, and/or (4) to switch the biochemical activity of specific proteins. Maternally loaded mRNAs are regulated primarily by a set of maternal RNA-binding proteins (RBPs), each of which binds to sometimes overlapping target sequences within the mRNA 3'UTRs and either promotes or inhibits translation. Most maternal transcripts are uniformly distributed throughout the embryo but specific transcripts are translated only in certain blastomeres. This control is achieved by the asymmetric distribution of the maternal RBPs, such that the blastomere-specific constellation of RBPs present, and their relative levels, determines the translational readout for their target transcripts. In certain well-studied cases, such as the specification of the sole endodermal precursor in the 8-cell embryo, the maternal transcripts and proteins along with their directly targeted zygotic genes have been identified.