Microglial cells are the resident macrophages in the central nervous system. These cells of mesodermal/mesenchymal origin migrate into all regions of the central nervous system, disseminate through the brain parenchyma, and acquire a specific ramified morphological phenotype termed "resting microglia." Recent studies indicate that even in the normal brain, microglia have highly motile processes by which they scan their territorial domains. By a large number of signaling pathways they can communicate with macroglial cells and neurons and with cells of the immune system. Likewise, microglial cells express receptors classically described for brain-specific communication such as neurotransmitter receptors and those first discovered as immune cell-specific such as for cytokines. Microglial cells are considered the most susceptible sensors of brain pathology. Upon any detection of signs for brain lesions or nervous system dysfunction, microglial cells undergo a complex, multistage activation process that converts them into the "activated microglial cell." This cell form has the capacity to release a large number of substances that can act detrimental or beneficial for the surrounding cells. Activated microglial cells can migrate to the site of injury, proliferate, and phagocytose cells and cellular compartments.

Physiology of Microglia

Degeneration and regeneration of the nervous system

The chemical senses—smell and taste—allow animals to evaluate and distinguish valuable food resources from dangerous substances in the environment. The central mechanisms by which the brain recognizes and discriminates attractive and repulsive odorants and tastants, and makes behavioral decisions accordingly, are not well understood in any organism. Recent molecular and neuroanatomical advances in Drosophila have produced a nearly complete picture of the peripheral neuroanatomy and function of smell and taste in this insect. Neurophysiological experiments have begun to provide insight into the mechanisms by which these animals process chemosensory cues. Given the considerable anatomical and functional homology in smell and taste pathways in all higher animals, experimental approaches in Drosophila will likely provide broad insights into the problem of sensory coding. Here we provide a critical review of the recent literature in this field and comment on likely future directions.

https://sites.oxy.edu/clint/physio/article/SmellandTasteinDrosophila.pdf

Molecular Architecture of Smell and Taste in Drosophila

The Cambrian appearance of fossils representing diverse phyla has long inspired hypotheses about possible genetic or environmental catalysts of early animal evolution. Only recently, however, have data begun to emerge that can resolve the sequence of genetic and morphological innovations, environmental events, and ecological interactions that collectively shaped Cambrian evolution. Assembly of the modern genetic tool kit for development and the initial divergence of major animal clades occurred during the Proterozoic Eon. Crown group morphologies diversified in the Cambrian through changes in the genetic regulatory networks that organize animal ontogeny. Cambrian radiation may have been triggered by environmental perturbation near the Proterozoic-Cambrian boundary and subsequently amplified by ecological interactions within reorganized ecosystems.

/pdf/early-animal-evolution-emerging-views-from-comparative-4wfpul73pd.pdf

Early Animal Evolution: Emerging Views from Comparative Biology and Geology

Tenascin, an extracellular matrix protein, is expressed in an unusually restricted pattern during embryogenesis and has been implicated in a variety of morphogenetic phenomena. To directly assess the function of tenascin in vivo, we generated mutant mice in which the tenascin gene was nully disrupted by replacing it with the lacZ gene. In mutant mice, lacZ was expressed in place of tenascin, and no tenascin product was detected. Homozygous mutant mice were, however, obtained in accordance with Mendelian laws, and both females and males produced offspring normally. No anatomical or histological abnormalities were detected in any tissues, and no major changes were observed in distribution of fibronectin, laminin, collagen, and proteoglycan. The existence of these mutant mice, lacking tenascin yet phenotypically normal, casts doubt on the theory that tenascin plays and essential role in normal development.

/pdf/mice-develop-normally-without-tenascin-1wq0cguvue.pdf

Mice develop normally without tenascin.

Mushroom bodies (MBs) are the centers for olfactory associative learning and elementary cognitive functions in the arthropod brain. In order to understand the cellular and genetic processes that control the early development of MBs, we have performed high-resolution neuroanatomical studies of the embryonic and post-embryonic development of the Drosophila MBs. In the mid to late embryonic stages, the pioneer MB tracts extend along Fasciclin II (FAS II)-expressing cells to form the primordia for the peduncle and the medial lobe. As development proceeds, the axonal projections of the larval MBs are organized in layers surrounding a characteristic core, which harbors bundles of actin filaments. Mosaic analyses reveal sequential generation of the MB layers, in which newly produced Kenyon cells project into the core to shift to more distal layers as they undergo further differentiation. Whereas the initial extension of the embryonic MB tracts is intact, loss-of-function mutations of fas II causes abnormal formation of the larval lobes. Mosaic studies demonstrate that FAS II is intrinsically required for the formation of the coherent organization of the internal MB fascicles. Furthermore, we show that ectopic expression of FAS II in the developing MBs results in severe lobe defects, in which internal layers also are disrupted. These results uncover unexpected internal complexity of the larval MBs and demonstrate unique aspects of neural generation and axonal sorting processes during the development of the complex brain centers in the fruit fly brain.

Embryonic and larval development of the Drosophila mushroom bodies: concentric layer subdivisions and the role of fasciclin II

The larval brain of Drosophila is a useful model to study olfactory processing because of its cellular simplicity. The early stages of central olfactory processing involve the detection of odor features, but the coding mechanisms that transform them into a representation in higher brain centers is not clear. Here we examine the pattern of connectivity of the main neurons that process olfactory information in the calyx (dendritic region) of the mushroom bodies, a higher brain center essential for associative olfactory learning. The larval calyx has a glomerular organization. We generated a map of calyx glomeruli, using both anatomical criteria and the pattern of innervation by subsets of its input neurons (projection neurons), molecularly identified by GAL4 markers. Thus, we show that projection neurons innervate calyx glomeruli in a stereotypic manner. By contrast, subsets of mushroom body neurons (Kenyon cells) that are labeled by GAL4 markers show no clear preference for specific glomeruli. Clonal subsets of Kenyon cells show some preference for subregions of the calyx, implying that they receive distinct input. However, at the level of individual glomeruli, dendritic terminals of larval-born Kenyon cells innervate about six glomeruli, apparently randomly. These results are consistent with a model in which Kenyon cells process olfactory information by integrating different inputs from several calyx glomeruli in a combinatorial manner.

https://www.pnas.org/content/pnas/102/52/19027.full.pdf

Stereotypic and random patterns of connectivity in the larval mushroom body calyx of Drosophila

Odor discrimination in higher brain centers is essential for behavioral responses to odors. One such center is the mushroom body (MB) of insects, which is required for odor discrimination learning. The calyx of the MB receives olfactory input from projection neurons (PNs) that are targets of olfactory sensory neurons (OSNs) in the antennal lobe (AL). In the calyx, olfactory information is transformed from broadly-tuned representations in PNs to sparse representations in MB neurons (Kenyon cells). However, the extent of stereotypy in olfactory representations in the calyx is unknown. Using the anatomically-simple larval olfactory system of Drosophila in which odor ligands for the entire set of 21 OSNs are known, we asked how odor identity is represented in the MB calyx. We first mapped the projections of all larval OSNs in the glomeruli of the AL, and then followed the connections of individual PNs from the AL to different calyx glomeruli. We thus established a comprehensive olfactory map from OSNs to a higher olfactory association center, at a single-cell level. Stimulation of single OSNs evoked strong neuronal activity in 1 to 3 calyx glomeruli, showing that broadening of the strongest PN responses is limited to a few calyx glomeruli. Stereotypic representation of single OSN input in calyx glomeruli provides a mechanism for MB neurons to detect and discriminate olfactory cues.

https://www.pnas.org/content/pnas/106/25/10314.full.pdf

Localized olfactory representation in mushroom bodies of Drosophila larvae

In a widely cited paper1, Slack et al. proposed that all animal phyla shared a particular pattern of gene expression, the “zootype”. The zootype hypothesis implies that at least six HOX-type homeobox-containing genes should be present in all metazoa. We have done a series of phylogenetic analyses which indicate that Cnidaria, thought to be the earliest-evolving animal phylum with the exception of the sponges2, lack several HOX genes that are present in Drosophila and vertebrates. Instead, these genes may have arisen by duplication after the origin of the Cnidaria.

Cnidarian homeoboxes and the zootype

The marine jellyfish Podocoryne carnea (Cnidaria, Hydrozoa) has a metagenic life cycle consisting of a larva, a colonial polyp and a free-swimming jellyfish (medusa). To study the function of HOX genes in primitive diploblastic animals we screened a library of P. carnea cDNA using PCR primers derived from the most conserved regions in helix 1 and helix 3 of the homeobox. A novel gene, Cnox2-Pc, has been isolated and characterized. Cnox2-Pc is a HOX cluster-like gene, and its homeodomain shows similarity to the Deformed subfamily of HOM-C/HOX genes. In situ hybridization revealed that Cnox2-Pc is expressed in the anterior region of the larva, the polyp head, and the most apical ectoderm of the differentiating bud during medusa development. In adult medusa expression is restricted to the gastrovascular entoderm. The results suggest that Cnox2-Pc is involved in establishment of an anterior-posterior axis during development in primitive metazoans.

Liria M. Masuda-Nakagawa

Papers

Embryonic and larval development of the Drosophila mushroom bodies: concentric layer subdivisions and the role of fasciclin II

Stereotypic and random patterns of connectivity in the larval mushroom body calyx of Drosophila

Localized olfactory representation in mushroom bodies of Drosophila larvae

Cnidarian homeoboxes and the zootype

The HOX-like gene Cnox2-Pc is expressed at the anterior region in all life cycle stages of the jellyfish Podocoryne carnea.