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First published online 16 April 2008
doi: 10.1242/dev.020180

Development 135, 1843-1851 (2008)
Published by The Company of Biologists 2008
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SoxB1 transcription factors and Notch signaling use distinct mechanisms to regulate proneural gene function and neural progenitor differentiation

Johan Holmberg1, Emil Hansson2, Michal Malewicz1, Magnus Sandberg1, Thomas Perlmann1, Urban Lendahl2 and Jonas Muhr1,*

1 Ludwig Institute for Cancer Research, Karolinska Institute, Box 240, SE-171 77 Stockholm, Sweden.
2 Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institute, SE-171 77 Stockholm, Sweden.

* Author for correspondence (e-mail: jonas.muhr{at}licr.ki.se)

Accepted 25 March 2008

The preservation of a pool of neural precursors is a prerequisite for proper establishment and maintenance of a functional central nervous system (CNS). Both Notch signaling and SoxB1 transcription factors have been ascribed key roles during this process, but whether these factors use common or distinct mechanisms to control progenitor maintenance is unsettled. Here, we report that the capacity of Notch to maintain neural cells in an undifferentiated state requires the activity of SoxB1 proteins, whereas the mechanism by which SoxB1 block neurogenesis is independent of Notch signaling. A common feature of Notch signaling and SoxB1 proteins is their ability to inhibit the activity of proneural bHLH proteins. Notch represses the transcription of proneural bHLH genes, while SoxB1 proteins block their neurogenic capacity. Moreover, E-proteins act as functional partners of proneural proteins and the suppression of E-protein expression is an important mechanism by which Notch counteracts neurogenesis. Interestingly, in contrast to the Hes-dependent repression of proneural genes, suppression of E-protein occurs in a Hes-independent fashion. Together, these data reveal that Notch signaling and SoxB1 transcription factors use distinct regulatory mechanisms to control proneural protein function and to preserve neural cells as undifferentiated precursors.

Key words: CNS development, Neurogenesis, Notch, Proneural bHLH proteins, Sox proteins


Related articles in Development:

Notch and Sox: different routes to progenitor maintenance

Development 2008 135: 104. [Full Text]  



This article has been cited by other articles:


Home page
 J. Cell Sci.Home page
J. Holmberg, E. Hansson, M. Malewicz, M. Sandberg, T. Perlmann, U. Lendahl, and J. Muhr
SoxB1 transcription factors and Notch signaling use distinct mechanisms to regulate proneural gene function and neural progenitor differentiation
J. Cell Sci., May 15, 2008; 121(10): e1007 - e1007.
[Full Text]


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