, 2002b). In addition, with maturation

retinal granule neurons undergo a switch from preferential axon growth to preferential dendrite growth (Goldberg et al., 2002b). Collectively, these observations suggest that neurons harbor developmentally inherited cell-intrinsic mechanisms that determine in large part neuronal morphogenesis. Transcriptional control of gene expression represents a major mode of cell-intrinsic regulation of neuronal development. Transcription factors can govern entire developmental programs, directing distinct stages of neuronal development as well as altering the competency and response of cells to extrinsic cues. Accordingly, often the expression of one or a set of transcription factors is sufficient to direct the subtype specification of distinct neuronal populations and thus their morphology and projection patterns (Arlotta et al., INCB28060 2005, Chen et al., 2005b, Hand et al., 2005, Lai et al., 2008, Liodis et al., 2007, Molyneaux et al., 2005, Molyneaux et al., 2007 and Polleux et al., 2007). The current challenge is to understand the extent of intrinsic regulation by identifying the transcription factors

responsible in different aspects of neuronal morphogenesis, their direct targets, and the interplay with extrinsic cues. Studies of the mammalian cerebellar cortex have highlighted the importance of transcription

factors in distinct aspects of neuronal morphogenesis and connectivity (Figure 1). learn more The rodent cerebellar cortex provides an excellent model system for the study of mechanisms that shape neurons (Altman and Bayer, 1997, Hatten, 1999, Palay and Chan-Palay, 1974 and Ramón y Cajal, 1995). Postmitotic granule neurons are generated after division of progenitors located in the external granule layer (EGL). A newly generated granule neuron first extends a single process along the molecular layer (ML). A second process is then generated at the opposite pole of the neuron, giving it a bipolar morphology. A phase of tangential migration follows as the bipolar processes continue to grow before the neuron generates a third leading process perpendicular Thymidine kinase to the plane of the ML that directs somal migration radially toward the internal granule layer (IGL). As the soma migrates inward in the cerebellar cortex, the two processes in the ML fuse while the neuron continues to extend a trailing process perpendicular to the plane of the ML. The intersection of these orthogonally oriented processes gives rise to the characteristic T-shaped parallel fiber axon of granule neurons. Once granule neurons reach the IGL, they begin to extend dendrites, which following pruning and maturation establish synaptic connections (Altman and Bayer, 1997 and Ramón y Cajal, 1995).