Embryonic neurogenesis is a critical event in brain development, in which various types of neurons are generated. During neurogenesis, the numbers and types of neurons produced must be precisely controlled to allow the proper formation of neural circuits and ultimately construction of a functional brain. Accordingly, impairments in embryonic neurogenesis can lead to the production of abnormal numbers and types of neurons, resulting in severe neurodevelopmental disorders such as microcephaly. Nonetheless, how the fate of neurons is determined during embryonic neurogenesis remains poorly understood. We found that the protein expression of the upper-layer but not the lower-layer neuronal marker is significantly decreased in cyclin-dependent kinase 5 knockout (cdk5^-/-) mouse brains...[ Read more ]

Embryonic neurogenesis is a critical event in brain development, in which various types of neurons are generated. During neurogenesis, the numbers and types of neurons produced must be precisely controlled to allow the proper formation of neural circuits and ultimately construction of a functional brain. Accordingly, impairments in embryonic neurogenesis can lead to the production of abnormal numbers and types of neurons, resulting in severe neurodevelopmental disorders such as microcephaly. Nonetheless, how the fate of neurons is determined during embryonic neurogenesis remains poorly understood. We found that the protein expression of the upper-layer but not the lower-layer neuronal marker is significantly decreased in cyclin-dependent kinase 5 knockout (cdk5^-/-) mouse brains at embryonic day 18, suggesting that Cdk5 may play a role in the regulation of neuronal fate specification during embryonic neurogenesis. Interestingly, according to in utero cdk5 conditional knockout experiments, the decreased expression of upper-layer neuronal markers is regulated by the specific knockout of Cdk5 in neural progenitors, suggesting that Cdk5 acts in neural progenitors to regulate the upper-layer neuronal fate specification in a cell-autonomous manner. We further found that Cdk5 affects upper-layer neuronal marker expression only at protein level, implicating that Cdk5 may regulate the upper-layer neuronal marker expression through post-transcriptional processes. In conclusion, our findings suggest that Cdk5 regulates cortical development through modulation of the protein levels of upper-layer neuronal markers. In the future, it will be interesting to investigate whether deletion of Cdk5 disrupts the differentiation of the upper-layer neurons in cerebral cortical development by reducing the expression of upper-layer neuronal markers. In addition, it is worth the effort to study the molecular mechanism that underlies the action of Cdk5 in embryonic neurogenesis.