Transcriptional cascade from Math1 to Mbh1 and Mbh2 is required for cerebellar granule cell differentiation

Developmental Biology
Daisuke Kawauchi, Tetsuichiro Saito

Abstract

Cerebellar granule cells (CGCs) are the most abundant neuronal type in the mammalian brain, and their differentiation is regulated by the basic helix-loop-helix gene, Math1. However, little is known about downstream genes of Math1 and their functions in the cerebellum. To investigate them, we have here established an electroporation-based in vivo gene transfer method in the developing mouse cerebellum. Misexpression of Math1 ectopically induced expression of Bar-class homeobox genes, Mbh1 and Mbh2, which are expressed by CGCs. Conversely, their expression was repressed in CGCs by knockdown of Math1. These findings, taken together with chromatin immunoprecipitation assays, suggest that Math1 directly regulates the Mbh genes in CGCs. Furthermore, a dominant-negative form of the Mbh proteins disrupted proper formation of the external granule layer and differentiation of CGCs, whereas misexpression of the Mbh genes ectopically induced expression of a CGC marker in nonneuronal cells, indicating that the Mbh proteins are required for the differentiation of CGCs.

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Citations

Feb 9, 2011·Proceedings of the National Academy of Sciences of the United States of America·Tiemo J KlischHuda Y Zoghbi
Feb 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Qian DingLin Gan
Jan 30, 2013·Journal of Neuroscience Methods·Tatsuya SatoTetsuichiro Saito
Apr 26, 2015·The Cerebellum·Lena Constantin, Brandon J Wainwright
Jul 11, 2012·The European Journal of Neuroscience·Jun NishiyamaMichisuke Yuzaki
Jun 9, 2016·Briefings in Functional Genomics·Marc ZuckermannJan Gronych
Oct 7, 2015·The Cerebellum·Ketty LetoRichard Hawkes
Oct 12, 2010·Expert Review of Neurotherapeutics·Adrian M DubucMichael D Taylor

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