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Vertebrate retina and hypothalamus development

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Abstract The vertebrate retina and hypothalamus, which emerge from adjacent regions of the ventral diencephalon, provide accessible experimental systems for analysis of the molecular mechanisms by which neuronal subtype diversity is specified, and how this neuronal subtype diversity regulates perception and behavior. Although the retina emerges as a lateral extension of the hypothalamus prior to the onset of neurogenesis, the retina and hypothalamus go on to eventually be comprised of almost entirely different cell types, and differ extensively in the spatial organization, function, and connectivity of these cells. Despite these differences in cell composition, there are a number of mechanistic and molecular similarities in the process of cell fate specification in both organs, including a stereotyped temporal sequence in which major cell types are generated. Although a handful of genes have been identified in both systems that direct cell fate specification, many more remain to be characterized, and large numbers of candidate genes have been identified in recent high‐throughput screens, particularly in retina. Experimental challenges for the near future include functional analysis of the genes identified so far, and the use of the molecular pathways gained from analysis of the development of specific neuronal lineages to study the contribution of these cells to perception and behavior. Copyright © 2009 John Wiley & Sons, Inc. This article is categorized under: Developmental Biology > Developmental Processes in Health and Disease

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(a) Secreted Shh from the prechordal plate patterns the ventral diencephalon. (b) Gene expression patterns in diencephalon prior to onset of neurogenesis and optic stalk extension. Diagram adapted from Levine and Green.5 (c) Extension of the optic stalk later separates retinal and hypothalamic neuroepithelium. Gene expression patterns are indicated for (b) and (c).

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Differentially expressed genes with similar expression patterns in bulk mRNA samples can have very different cellular expression patterns. Three hypothetical examples from retina are shown. Low and high expression levels of genes A and C are indicated. ONBL, outer neuroblastic layer; INBL, inner neuroblastic layer; ONL, outer nuclear layer; INL, inner nuclear layer; GCL, ganglion cell layer; and OPL, outer plexiform layer.

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(a) Transcription factors required for the development of specific retinal cell types are indicated. (b) Genes selectively expressed in developing specific hypothalamic nuclei are indicated. Gene names in bold indicate transcription factors, while italics indicate neuropeptides. SCN, suprachiasmatic nucleus; POA, preoptic area; AH, anterior hypothalamus; PVN, paraventricular nucleus; SON, supraoptic nucleus; DMH, dorsomedial hypothalamus; VMH, ventromedial hypothalamus; ARC, arcuate nucleus; PH, posterior hypothalamus; LH, lateral hypothalamus; MB, mammilary body; OT, oxytocin; AVP, arginine vasopressin; CRH, corticotropin‐releasing hormone; TRH, thyrotropin‐releasing hormone, NPY, neuropeptide Y; AGRP, agouti gene‐related peptide; CART, cocaine and amphetamine‐regulated transcript; POMC, proopiomelanocortin; and LHRH, luteinizing hormone‐releasing hormone.

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