RORalpha coordinates reciprocal signaling in cerebellar development through sonic hedgehog and calcium-dependent pathways.

ABSTRACT: The cerebellum provides an excellent system for understanding how afferent and target neurons coordinate sequential intercellular signals and cell-autonomous genetic programs in development. Mutations in the orphan nuclear receptor RORalpha block Purkinje cell differentiation with a secondary loss of afferent granule cells. We show that early transcriptional targets of RORalpha include both mitogenic signals for afferent progenitors and signal transduction genes required to process their subsequent synaptic input. RORalpha acts through recruitment of gene-specific sets of transcriptional cofactors, including beta-catenin, p300, and Tip60, but appears independent of CBP. One target promoter is Sonic hedgehog, and recombinant Sonic hedgehog restores granule precursor proliferation in RORalph

SUBMITTER: Gold DA 

PROVIDER: S-EPMC2717708 | biostudies-literature | 2003 Dec

REPOSITORIES: biostudies-literature