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SMAD4 is essential for generating subtypes of neurons during cerebellar development

SMAD4 is essential for generating subtypes of neurons during cerebellar development
Cerebellum development involves the coordinated production of multiple neuronal cell types. The cerebellar primordium contains two germinative zones, the rhombic lip (RL) and the ventricular zone (VZ), which generate different types of glutamatergic and GABAergic neurons, respectively. What regulates the specification and production of glutamatergic and GABAergic neurons as well as the subtypes for each of these two broad classes remains largely unknown. Here we demonstrate with conditional genetic approaches in mice that SMAD4, a major mediator of BMP and TGFβ signaling, is required early in cerebellar development for maintaining the RL and generating subsets of RL-derived glutamatergic neurons, namely neurons of the deep cerebellar nuclei, unipolar brush cells, and the late cohort of granule cell precursors (GCPs). The early cohort of GCPs, despite being deficient for SMAD4, is still generated. In addition, the numbers of GABAergic neurons are reduced in the mutant and the distribution of Purkinje cells becomes abnormal. These studies demonstrate a temporally and spatially restricted requirement for SMAD4 in generating subtypes of cerebellar neurons.
- Albert Einstein College of Medicine United States
- Yeshiva University United States
Neurons, Mouse, Cell Differentiation, Cell Biology, SMAD4, Deep cerebellar nuclei, Mice, Purkinje Cells, Unipolar brush cells, Cerebellar Nuclei, Transforming Growth Factor beta, Cerebellum, Animals, Granule cell precursor, Molecular Biology, Rhombic lip, Developmental Biology, Smad4 Protein
Neurons, Mouse, Cell Differentiation, Cell Biology, SMAD4, Deep cerebellar nuclei, Mice, Purkinje Cells, Unipolar brush cells, Cerebellar Nuclei, Transforming Growth Factor beta, Cerebellum, Animals, Granule cell precursor, Molecular Biology, Rhombic lip, Developmental Biology, Smad4 Protein
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