The mechanism of Histone Deacetylase 1 function in specification of neural fates in the developing zebrafish CNS. (360G-Wellcome-081884_Z_07_Z)

Hdac1 is essential for transformation of neural progenitors in the developing zebrafish CNS into differentiated neurons and oligodendrocytes. The overall aim is to elucidate how Hdac1 exerts direct transcriptional control over this process. It remains unclear if Hdac1 functions in proliferating neural progenitors, in the post-mitotic descendants of neural progenitors, or if Hdac1 is required in both of these CNS compartments. Moreover, the spectrum of target genes that are subject to Hdac1-depen dent transcriptional control in the CNS is unknown, as are key features of the epigenetic control mechanisms modulated by Hdac1 function. Accordingly, the project has the following key goals: 1. To rescue the neural defects in the hdac1 mutant CNS using stably integrated transgenes which target Hdac1 function to proliferating neural progenitors, their post-mitotic progeny, or both CNS compartments. 2. To identify sets of genes (a) that are directly repressed by Hdac1 and (b) whose expr ession is Hdac1-dependent, in the developing CNS 3. To identify direct interactions between Hdac1 and cis-regulatory elements of target genes. 4. To elucidate the Hdac1-dependent changes in the patterns of chromatin modifications associated with promoters of genes that are regulated by Hdac1 function in the developing CNS.