Rather, Bhlhb5 belongs to a subfamily of bHLH factors including Bhlhb4 (also known as Bhlhe23) and the Olig proteins (Olig1-3) that function predominantly as transcriptional repressors. As an example, when Olig2 is fused to the repressor domain of Engrailed, this fusion protein, but not an activating Olig2-VP16 fusion protein, recapitulates the function of native Olig2 by specifying neural fate in the chick spinal cord (Zhou and Anderson,

2002). Bhlhb5 and Fludarabine Bhlhb4 are likewise thought to mediate repression based on their ability to inhibit the transactivation of NeuroD-responsive target genes in luciferase assays (Bramblett et al., 2002, Peyton et al., 1996 and Xu et al., 2002). http://www.selleckchem.com/Androgen-Receptor.html However, while these findings suggest that the Oligs, Bhlhb4, and Bhlhb5 form a subfamily of bHLH factors that mediate transcriptional repression, the manner in which these repressors function endogenously

to repress transcription and orchestrate neural circuit development remains obscure. Studies in the spinal cord have provided a framework for understanding the cellular function of Olig proteins, and these studies suggest that a common function of the Oligs is to confer the neuronal identity of neural progenitors. For instance, Olig1 and Olig2 are expressed in select progenitors of the ventral spinal cord and, in the absence of these factors, neural precursors are respecified to an alternate fate: instead of forming motor neurons and oligodendrocytes, these pMN progenitors inappropriately generate V2 interneurons and astrocytes (Lu et al., 2002, Takebayashi et al., 2002 and Zhou and Anderson, 2002). It is thought that this type of misspecification occurs because the Oligs function, at least in part, to promote

the generation of one subtype of neuron over another by inhibiting the expression of transcription factors that mediate the alternative cell fate choices (Marquardt and Pfaff, 2001). Though Bhlhb4 and Bhlhb5 are closely else related to the Oligs, their expression is almost exclusively limited to postmitotic neurons rather than proliferating neural progenitors, hinting at the possibility that Bhlhb4 and Bhlhb5 regulate later aspects of neuronal differentiation (Bramblett et al., 2002, Joshi et al., 2008 and Ross et al., 2010). Further evidence in support of this idea comes from studies in the retina where loss of either Bhlhb4 or Bhlhb5 results not in the misspecification of retinal progenitors to alternate fates but rather the loss of subsets of neurons, presumably due to apoptosis. Thus, mice lacking Bhlhb4 have an absence of rod bipolar cells, whereas Bhlhb5 mutants are lacking cone bipolar and selective amacrine cells ( Bramblett et al., 2004 and Feng et al., 2006).