Proneural Genes and Cerebellar Neurogenesis in the Ventricular Zone and Upper Rhombic Lip
The cerebellar primordium arises between embryonic days 8.5 and 9.5 from dorsal rhombomere 1, adjacent to the fourth ventricle. Cerebellar patterning requires the concerted action of morphogens secreted by the rhombic lip and roof plate, and leads to the
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Proneural Genes and Cerebellar Neurogenesis in the Ventricular Zone and Upper Rhombic Lip G. Giacomo Consalez, Marta Florio, Luca Massimino, and Laura Croci
Abstract
The cerebellar primordium arises between embryonic days 8.5 and 9.5 from dorsal rhombomere 1, adjacent to the fourth ventricle. Cerebellar patterning requires the concerted action of morphogens secreted by the rhombic lip and roof plate, and leads to the formation of two main neurogenetic centers, the upper rhombic lip and ventricular zone, from which glutamatergic and GABAergic neurons arise, respectively. These territories contain gene expression microdomains that are partially overlapping and, among others, express proneural genes. This gene family is tightly conserved in evolution and encodes basic helix-loop-helix transcription factors implicated in many neurogenetic events, ranging from cell-fate specification to terminal differentiation of a variety of neuronal types across the embryonic nervous system. The present paper deals with the established or suggested roles of proneural genes in cerebellar neurogenesis. Of the proneural genes examined in this chapter, Atoh1 plays a quintessential role in the specification and development of granule cells and other cerebellar glutamatergic neurons. Besides playing key roles at early stages in these early developmental events, Atoh1 is a key player in the clonal expansion of GC progenitors of the external granule layer. NeuroD, formerly regarded as a proneural gene, acts as a master gene in granule cell differentiation, survival, and dendrite formation. Ascl1 participates in GABA interneuron and cerebellar nuclei neurons generation, and suppresses astrogliogenesis. Conversely, little is known to date about the role(s) of Neurog1 and Neurog2 in cerebellar neurogenesis, and a combination of loss- and gain-of-function studies is required to elucidate their role, if any, in cerebellar neurogenesis.
G.G. Consalez (*) • M. Florio • L. Massimino • L. Croci Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, Milan, 20132, Italy e-mail: [email protected], [email protected], [email protected], [email protected] M. Manto, D.L. Gruol, J.D. Schmahmann, N. Koibuchi, F. Rossi (eds.), Handbook of the Cerebellum and Cerebellar Disorders, DOI 10.1007/978-94-007-1333-8_2, # Springer Science+Business Media Dordrecht 2013
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Introduction The mature cerebellum represents only 10% of the total brain volume, but contains the majority (80–85%) of human neurons (reviewed in Herrup and Kuemerle 1997). It is the primary center of motor coordination and it is essential for cognitive processing and sensory discrimination (Schmahmann 2004). In humans, the cerebellum achieves its mature configuration only many months after birth and for this reason it is especially vulnerable to developmental abnormalities. Like the cerebrum, the cerebellum comprises an outer cortical structure, a layer of white matter, and a set of cerebellar nuclei (CN) beneath the white matter. T
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