Elsevier

Developmental Biology

Volume 322, Issue 2, 15 October 2008, Pages 345-354
Developmental Biology

Genomes & Developmental Control
Transcriptional cascade from Math1 to Mbh1 and Mbh2 is required for cerebellar granule cell differentiation

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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.

Keywords

Cerebellar granule cells
Purkinje cells
Basic helix-loop-helix
Homeobox
Math1
Ptf1a
Mbh1
Mbh2
In vivo electroporation

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