The generation of functionally distinct neuronal subtypes within the vertebrate 
central nervous system (CNS) requires the precise regulation of progenitor gene 
expression in specific neuronal territories during early embryogenesis. 
Accumulating evidence has implicated histone deacetylase (HDAC) proteins in cell 
specification, proliferation, and differentiation in diverse embryonic and adult 
tissues. However, although HDAC proteins have shown to be expressed in the 
developing vertebrate neural tube, their specific role in CNS neural progenitor 
fate specification remains unclear. Prior work from our lab showed that the 
Tcf7l2/Tcf4 transcription factor plays a key role in ventral progenitor lineage 
segregation by differential repression of two key specification factors, Nkx2.2 
and Olig2. In this study, we found that administration of HDAC inhibitors 
(Valproic Acid (VPA), Trichostatin-A (TSA), or sodium butyrate) in chick embryos 
in ovo disrupted normal progenitor gene segregation in the developing neural 
tube, indicating that HDAC activity is required for this process. Further, using 
functional and pharmacological approaches in vivo, we found that HDAC activity 
is required for the differential repression of Nkx2.2 and Olig2 by Tcf7l2/Tcf4. 
Finally, using dominant-negative functional assays, we provide evidence that 
Tcf7l2/Tcf4 repression also requires Gro/TLE/Grg co-repressor factors. Together, 
our data support a model where the transcriptional repressor activity of 
Tcf7l2/Tcf4 involves functional interactions with both HDAC and Gro/TLE/Grg 
co-factors at specific target gene regulatory elements in the developing neural 
tube, and that this activity is required for the proper segregation of the 
Nkx2.2 (p3) and Olig2 (pMN) expressing cells from a common progenitor pool.