Sonic hedgehog and notch signaling can cooperate to regulate neurogenic divisions of neocortical progenitors

Dave, Richa K., Ellis, Tammy, Toumpas, Melissa C., Robson, Jonathan P., Julian, Elaine, Adolphe, Christelle, Bartlett, Perry F., Cooper, Helen M., Reynolds, Brent A. and Wainwright, Brandon J. (2011) Sonic hedgehog and notch signaling can cooperate to regulate neurogenic divisions of neocortical progenitors. PLoS One, 6 2: e14680-1-e14680-13. doi:10.1371/journal.pone.0014680

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Author Dave, Richa K.
Ellis, Tammy
Toumpas, Melissa C.
Robson, Jonathan P.
Julian, Elaine
Adolphe, Christelle
Bartlett, Perry F.
Cooper, Helen M.
Reynolds, Brent A.
Wainwright, Brandon J.
Title Sonic hedgehog and notch signaling can cooperate to regulate neurogenic divisions of neocortical progenitors
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2011-02
Sub-type Article (original research)
DOI 10.1371/journal.pone.0014680
Open Access Status DOI
Volume 6
Issue 2
Start page e14680-1
End page e14680-13
Total pages 13
Place of publication San Francisco, CA, U.S.A
Publisher Public Library of Science
Collection year 2012
Language eng
Formatted abstract
Background: Hedgehog (Hh) signaling is crucial for the generation and maintenance of both embryonic and adult stem cells, thereby regulating development and tissue homeostasis. In the developing neocortex, Sonic Hedgehog (Shh) regulates neural progenitor cell proliferation. During neurogenesis, radial glial cells of the ventricular zone (VZ) are the predominant neocortical progenitors that generate neurons through both symmetric and asymmetric divisions. Despite its importance, relatively little is known of the molecular pathways that control the switch from symmetric proliferative to differentiative/neurogenic divisions in neural progenitors.

Principal Findings:
Here, we report that conditional inactivation of Patched1, a negative regulator of the Shh pathway, in Nestin positive neural progenitors of the neocortex leads to lamination defects due to improper corticogenesis and an increase in the number of symmetric proliferative divisions of the radial glial cells. Hedgehog-activated VZ progenitor cells demonstrated a concomitant upregulation of Hes1 and Blbp, downstream targets of Notch signaling. The Notch signaling pathway plays a pivotal role in the maintenance of stem/progenitor cells and the regulation of glial versus neuronal identity. To study the effect of Notch signaling on Hh-activated neural progenitors, we inactivated both Patched1 and Rbpj, a transcriptional mediator of Notch signaling, in Nestin positive cells of the neocortex.

Our data indicate that by mid neurogenesis (embryonic day 14.5), attenuation of Notch signaling reverses the effect of Patched1 deletion on neurogenesis by restoring the balance between symmetric proliferative and neurogenic divisions. Hence, our results demonstrate that correct corticogenesis is an outcome of the interplay between the Hh and Notch signaling pathways.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

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Created: Sun, 06 Mar 2011, 00:03:39 EST