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WIREs Dev Biol
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Emergence of neuronal diversity from patterning of telencephalic progenitors

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During central nervous system (CNS) development, hundreds of distinct neuronal subtypes are generated from a single layer of multipotent neuroepithelial progenitor cells. Within the rostral CNS, initial regionalization of the telencephalon marks the territories where the cerebral cortex and the basal ganglia originate. Subsequent refinement of the primary structures determines the formation of domains of differential gene expression, where distinct fate‐restricted progenitors are located. To understand how diversification of neural progenitors and neurons is achieved in the telencephalon, it is important to address early and late patterning events in this context. In particular, important questions include: How does the telencephalon become specified and regionalized along the major spatial axes? Within each region, are the differences in neuronal subtypes established at the progenitor level or at the postmitotic stage? If distinct progenitors exist that are committed to subtype‐specific neuronal lineages, how does the diversification emerge? What is the contribution of positional and temporal cues and how is this information integrated into the intrinsic programs of cell identity? WIREs Dev Biol 2015, 4:197–214. doi: 10.1002/wdev.174 This article is categorized under: Establishment of Spatial and Temporal Patterns > Repeating Patterns and Lateral Inhibition Gene Expression and Transcriptional Hierarchies > Cellular Differentiation Nervous System Development > Vertebrates: Regional Development
Early telencephalic patterning and patterning centers. (a) Schematic view of the developing neural tube, showing the main subdivisions. A series of vesicles later give rise to the structures within the forebrain, midbrain, and hindbrain, with the telencephalic territory being specified in the most rostral regions of the prosencephalon. (b) Expansion and folding of the cephalic end of the neural tube determine the formation of the cerebral hemispheres. Neural progenitor cells within the telencephalon acquire a positional identity through the concerted action of patterning centers that release various morphogen signals. The hem, anti‐hem, prechordal plate, and anterior neural ridge (ANR) are illustrated on the diagram, along with examples of secreted morphogens as described in the main text. (c) Coronal section of the forebrain, illustrating the location of the hem and anti‐hem in relation to the developing dorsal and ventral telencephalon. These regions are characterized by differential expression of transcription factors that are indicated on the right.
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Development of the ventral forebrain. (a) Basic organization of the embryonic brain to illustrate the spatial location of the medial (MGE), lateral (LGE), and caudal (CGE) ganglionic eminences. Anterior and posterior cross‐sections of the forebrain are shown in b and c, respectively. (b) Coronal view of one cerebral hemisphere at a rostral level, illustrating the mediolateral position of the LGE and MGE. Differential expression of transcription factors between GEs and within GEs is illustrated by different color codes. These regions ultimately generate different neuronal populations, as indicated in the text below the figures. (c) Cross‐sectional view of one cerebral hemisphere at a caudal level, showing the site of origin of 30% of cortical interneurons.
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Cortical arealization and graded expression of transcription factors. (a) Schematic representation of the relative size and position of the four main functional areas of the cortex. M1, motor; S1, somatosensory; A1, auditory; V1, primary visual cortex. (b) Schematic view of the developing telencephalon, illustrating the gradient of expression of four transcription factors with patterning activity. Emx2–Pax6 and COUP‐TFI–Sp8 exhibit overlapping countergradients that establish cortical area identities along the major spatial axes. A, anterior; P, posterior; L, lateral; M, medial. (c) Summary of the changes in area patterning observed in genetic knockout animals of the specified transcription factors. See text for details and references.
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Gene Expression and Transcriptional Hierarchies > Cellular Differentiation
Nervous System Development > Vertebrates: Regional Development
Establishment of Spatial and Temporal Patterns > Repeating Patterns and Lateral Inhibition