 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
The Journal of Neuroscience, October 25, 2006, 26(43):11061-11071; doi:10.1523/JNEUROSCI.1358-06.2006
Previous Article | Next Article
Cellular/Molecular
Hes6 Inhibits Astrocyte Differentiation and Promotes Neurogenesis through Different Mechanisms
Sumit Jhas, Sorana Ciura, * Stephanie Belanger-Jasmin, * Zhifeng Dong, Estelle Llamosas, Francesca M. Theriault, Kerline Joachim, Yeman Tang, Lauren Liu, Jisheng Liu, andStefano Stifani Center for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A 2B4
Correspondence should be addressed to Stefano Stifani, Montreal Neurological Institute, 3801 rue University, Montreal, Quebec, Canada H3A 2B4. Email: stefano.stifani{at}mcgill.ca
The mechanisms regulating the generation of cell diversity in the mammalian cerebral cortex are beginning to be elucidated. In that regard, Hairy/Enhancer of split (Hes) 1 and 5 are basic helix-loop-helix (bHLH) factors that inhibit the differentiation of pluripotent cortical progenitors into neurons. In contrast, a related Hes family member termed Hes6 promotes neurogenesis. It is shown here that knockdown of endogenous Hes6 causes supernumerary cortical progenitors to differentiate into cells that exhibit an astrocytic morphology and express the astrocyte marker protein GFAP. Conversely, exogenous Hes6 expression in cortical progenitors inhibits astrocyte differentiation. The negative effect of Hes6 on astrocyte differentiation is independent of its ability to promote neuronal differentiation. We also show that neither its proneuronal nor its anti-gliogenic functions appear to depend on Hes6 ability to bind to DNA via the basic arm of its bHLH domain. Both of these activities require Hes6 to be localized to nuclei, but only its anti-gliogenic function depends on two short peptides, LNHLL and WRPW, that are conserved in all Hes6 proteins. These findings suggest that Hes6 is an important regulator of the neurogenic phase of cortical development by promoting the neuronal fate while suppressing astrocyte differentiation. They suggest further that separate molecular mechanisms underlie the proneuronal and anti-gliogenic activities of Hes6 in cortical progenitor cells.
Key words: astrocyte; cortical development; Groucho; Hes6; LXXLL motif; neurogenesis
Received March 30, 2006; revised Aug. 23, 2006; accepted Sept. 14, 2006.
Correspondence should be addressed to Stefano Stifani, Montreal Neurological Institute, 3801 rue University, Montreal, Quebec, Canada H3A 2B4. Email: stefano.stifani{at}mcgill.ca
This article has been cited by other articles:
C. S. Tremblay, C. C. Huard, F.-F. Huang, O. Habi, V. Bourdages, G. Levesque, and M. Carreau
The Fanconi Anemia Core Complex Acts as a Transcriptional Co-regulator in Hairy Enhancer of Split 1 Signaling
J. Biol. Chem., May 15, 2009; 284(20): 13384 - 13395.
[Abstract] [Full Text] [PDF]
E. K. Lee, G.-U. Bae, J. S. You, J. C. Lee, Y. J. Jeon, J. W. Park, J. H. Park, S. H. Ahn, Y. K. Kim, W. S. Choi, et al.
Reversine Increases the Plasticity of Lineage-committed Cells toward Neuroectodermal Lineage
J. Biol. Chem., January 30, 2009; 284(5): 2891 - 2901.
[Abstract] [Full Text] [PDF]
M. Buscarlet, A. Perin, A. Laing, J. M. Brickman, and S. Stifani
Inhibition of Cortical Neuron Differentiation by Groucho/TLE1 Requires Interaction with WRPW, but Not Eh1, Repressor Peptides
J. Biol. Chem., September 5, 2008; 283(36): 24881 - 24888.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|