<p>Tlx3 (HOX11L2) is regarded as one of the selector genes in excitatory versus inhibitory fate specification of neurons in distinct regions of the nervous system. Expression of Tlx3 in a post-mitotic immature neuron favors a glutamatergic over GABAergic fate. The factors that regulate Tlx3 have immense importance in the fate specification of glutamatergic neurons. Here, we have shown that Notch target gene, Hes-1, negatively regulates Tlx3 expression, resulting in decreased generation of glutamatergic neurons. Down-regulation of Hes-1 removed the inhibition on Tlx3 promoter, thus promoting glutamatergic differentiation. Promoter-protein interaction studies with truncated/mutated Hes-1 protein suggested that the co-repressor recruitment mediated through WRPW domain of Hes-1 has contributed to the repressive effect. Our results clearly demonstrate a new and unique role for canonical Notch signaling through Hes-1, in neurotransmitter/subtype fate specification of neurons in addition to its known functional role in proliferation/maintenance of neural progenitors.</p>
Dr. Indulekha C. L. Pillai, Divya, T. Sheela, Divya, M. Sivaraman, Sanalkumar, R., Rasheed, V. Abdul, Dhanesh, S. Bindu, Sebin, A., George, A., and James, J., “Hes-1 regulates the excitatory fate of neural progenitors through modulation of Tlx3 (HOX11L2) expression”, Cell Mol Life Sci, vol. 69, no. 4, pp. 611-27, 2012.