Chapter 1 Functional cloning of candidate genes that regulate Purkinje cell-specific gene expression

Abstract

Publisher Summary The bHLH family of transcription factors is key developmental modulators controlling cell fate in both vertebrate and invertebrate systems. The proneural genes achaete-scute (AS-C) and daughterless, for example, are the key regulators of neuronal cell fate in drosophila. Likewise, the role of bHLH proteins in vertebrate neurogenesis is partially elucidated by gene knock out experiments in mice. Persistent expression of HES-1—a mammalian homolog of the drosophila enhancer of split gene—disrupts neuronal and glial differentiation. Furthermore, targeted disruption of HES-1 leads to premature neurogenesis and neural defects in mice. The messenger RNA (mRNA) for ME2 is highly enriched in the brain relative to other tissues, detectable in the cerebellum throughout development, and appears to be expressed transiently in cerebellar Purkinje cells, but expression switches predominantly to granule cells postnatally. The chapter shows that ME2 can bind specifically to the L7-ATE and that it can activate transcription from tandem multimers of this element attached to an exogenous promoter.