A 3D molecular map of the cavefish neural plate illuminates eyefield organization and its borders in vertebrates
TL;DR: In this article, a comparative 3D expression map at the end of gastrulation/onset of neurulation was drawn, which highlights hyper-regionalization of the eyefield into sub-territories of distinct sizes, shapes, cell identities and putative fates along the three body axes.
Abstract: The vertebrate retinas originate from a specific anlage in the anterior neural plate called the eyefield. The eyefield shares its anterior border with the prospective telencephalon and is in contact ventrally and posteriorly with hypothalamic and diencephalic precursors. Eyefield identity is conferred by a set of "eye transcription factors", whose combinatorial expression has not been precisely characterized. Here, we use the dimorphic teleost species Astyanax mexicanus, which develops proper eyes in the wild type and smaller colobomatous eyes in the blind cavefish embryo, to unravel the molecular anatomy of the eyefield and its micro-evolutionary variations in the two Astyanax morphs. Using a series of markers (Rx3, Pax6, CxCr4b, Zic1, Lhx2, Emx3, Nkx2.1), we draw a comparative 3D expression map at the end of gastrulation/onset of neurulation, which highlights hyper-regionalization of the eyefield into sub-territories of distinct sizes, shapes, cell identities and putative fates along the three body axes. We also discover sub-domains within the prospective telencephalon, and we characterize cell identities at the frontiers of the eyefield. Analyses at the tissue scale and single cell level show variations in volumes and shapes of eyefield subdivisions as well as cellular gene expression levels and identity changes in cavefish. The ventro-medial border and the anterior border of the eyefield contain cells co-expressing hypothalamic and telencephalic marker, respectively, in cavefish embryos. Altogether, we provide a new model of eyefield patterning in 3D and suggest a developmental origin for the emergence of the coloboma phenotype in the natural mutant cavefish embryo.
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TL;DR: In this paper, the authors have deciphered the sequence of defective events leading to coloboma in the embryonic eye of the blind cavefish of the species Astyanax mexicanus.
Abstract: The morphogenesis of the vertebrate eye consists of a complex choreography of cell movements, tightly coupled to axial regionalization and cell type specification processes. Disturbances in these events can lead to developmental defects and blindness. Here, we have deciphered the sequence of defective events leading to coloboma in the embryonic eye of the blind cavefish of the species Astyanax mexicanus. Using comparative live imaging on targeted enhancer-trap Zic1:hsp70:GFP reporter lines of both the normal, river-dwelling morph and the cave morph of the species, we identified defects in migratory cell behaviors during evagination which participate in the reduced optic vesicle size in cavefish, without proliferation defect. Further, impaired optic cup invagination shifts the relative position of the lens and contributes to coloboma in cavefish. Based on these results, we propose a developmental scenario to explain the cavefish phenotype and discuss developmental constraints to morphological evolution. The cavefish eye appears as an outstanding natural mutant model to study molecular and cellular processes involved in optic region morphogenesis.
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TL;DR: Fiji is a distribution of the popular open-source software ImageJ focused on biological-image analysis that facilitates the transformation of new algorithms into ImageJ plugins that can be shared with end users through an integrated update system.
Abstract: Fiji is a distribution of the popular open-source software ImageJ focused on biological-image analysis. Fiji uses modern software engineering practices to combine powerful software libraries with a broad range of scripting languages to enable rapid prototyping of image-processing algorithms. Fiji facilitates the transformation of new algorithms into ImageJ plugins that can be shared with end users through an integrated update system. We propose Fiji as a platform for productive collaboration between computer science and biology research communities.
43,540 citations
TL;DR: The synthesis of information from fate mapping and experimental embryological and genetic studies is illuminating the mechanisms that generate the different components of the forebrain.
Abstract: ▪ Abstract Recent embryological studies are beginning to establish that the underlying organization of the forebrain may be reduced to relatively simple elements that are common to all vertebrates. We begin this chapter by reviewing studies that describe the similarities in prospective fate and molecular organization of the developing neural plate in fish, frogs, chickens, and mice. The chapter next addresses mechanisms that regulate regional specification in the anterior central nervous system. There is now evidence that the axial mesendoderm anterior to the notochord (the prechordal plate) has a central role in induction of the floor and basal plate primordia (hypothalamus) of the forebrain. Patterning of the anterolateral neural plate (telencephalon) may be regulated by FGF8 produced in the anterior neural ridge. Thus, the synthesis of information from fate mapping and experimental embryological and genetic studies is illuminating the mechanisms that generate the different components of the forebrain.
520 citations
TL;DR: The results support a model of progressive tissue specification in which neural induction then Otx2-driven neural patterning primes the anterior neural plate for eye field formation and form a self-regulating feedback network that specifies the vertebrate eye field.
Abstract: Several eye-field transcription factors (EFTFs) are expressed in the anterior region of the vertebrate neural plate and are essential for eye formation. The Xenopus EFTFs ET, Rx1, Pax6, Six3, Lhx2, tll and Optx2 are expressed in a dynamic, overlapping pattern in the presumptive eye field. Expression of an EFTF cocktail with Otx2 is sufficient to induce ectopic eyes outside the nervous system at high frequency. Using both cocktail subsets and functional (inductive) analysis of individual EFTFs, we have revealed a genetic network regulating vertebrate eye field specification. Our results support a model of progressive tissue specification in which neural induction then Otx2-driven neural patterning primes the anterior neural plate for eye field formation. Next, the EFTFs form a self-regulating feedback network that specifies the vertebrate eye field. We find striking similarities and differences to the network of homologous Drosophila genes that specify the eye imaginal disc, a finding that is consistent with the idea of a partial evolutionary conservation of eye formation.
507 citations
TL;DR: The function of Lhx2, a LIM homeobox gene expressed in developing B-cells, forebrain and neural retina, is investigated by analyzing embryos deficient in functional Lx2 protein, finding it necessary for normal development of the eye, cerebral cortex, and efficient definitive erythropoiesis.
Abstract: We investigated the function of Lhx2, a LIM homeobox gene expressed in developing B-cells, forebrain and neural retina, by analyzing embryos deficient in functional Lhx2 protein. Lhx2 mutant embryos are anophthalmic, have malformations of the cerebral cortex, and die in utero due to severe anemia. In Lhx2−/− embryos specification of the optic vesicle occurs; however, development of the eye arrests prior to formation of an optic cup. Deficient cellular proliferation in the forebrain results in hypoplasia of the neocortex and aplasia of the hippocampal anlagen. In addition to the central nervous system malformations, a cell non-autonomous defect of definitive erythropoiesis causes severe anemia in Lhx2−/− embryos. Thus Lhx2 is necessary for normal development of the eye, cerebral cortex, and efficient definitive erythropoiesis.
484 citations
TL;DR: Early events in forebrain development are discussed--those that lead to the establishment of the anterior neural plate and the regional subdivision of this territory into the different domains of the prospective forebrain.
443 citations