Ptch1-mediated dosage-dependent action of Shh signaling regulates neural progenitor development at late gestational stages

Shikata, Yayoi, Okada, Toshiaki, Hashimoto, Mitsuhiro, Ellis, Tammy L., Matsumaru, Daisuke, Shiroishi, Toshihiko, Ogawa, Masaharu, Wainwright, Brandon J. and Motoyama, Jun (2011) Ptch1-mediated dosage-dependent action of Shh signaling regulates neural progenitor development at late gestational stages. Developmental Biology, 349 2: 147-159. doi:10.1016/j.ydbio.2010.10.014


Author Shikata, Yayoi
Okada, Toshiaki
Hashimoto, Mitsuhiro
Ellis, Tammy L.
Matsumaru, Daisuke
Shiroishi, Toshihiko
Ogawa, Masaharu
Wainwright, Brandon J.
Motoyama, Jun
Title Ptch1-mediated dosage-dependent action of Shh signaling regulates neural progenitor development at late gestational stages
Journal name Developmental Biology   Check publisher's open access policy
ISSN 0012-1606
1095-564X
Publication date 2011-01-15
Year available 2010
Sub-type Article (original research)
DOI 10.1016/j.ydbio.2010.10.014
Volume 349
Issue 2
Start page 147
End page 159
Total pages 13
Place of publication Maryland Heights, MO, U.S.A.
Publisher Academic Press
Collection year 2012
Language eng
Formatted abstract
Sonic hedgehog (Shh) signaling regulates cell differentiation and proliferation during brain development. However, the role of Shh in neurogenesis during late gestation (embryonic day 13.5-18.5) remains unclear. Herein, we used a genetic approach and in utero electroporation to investigate the role of mouse Shh and patched homolog 1 (Ptch1), the putative receptor for Shh. Proliferating cortical intermediate (basal) progenitor cells (IPCs) were severely reduced in Shh mutant mice, suggesting that endogenous Shh signaling could play an essential role in cortical IPC development. During cortical neurogenesis, strong upregulation of Shh signaling enhanced the transition from ventricular zone (VZ) progenitors to ventralized IPCs, while low levels of signaling enhanced the generation and proliferation of cortical IPCs in the subventricular zone. The effects of Shh upregulation in this study were consistent with a phenotype of conditional loss of function of Ptch1, and the phenotype of a hypomorphic allele of Ptch1, respectively. These data indicated that endogenous Ptch1 mediates the broad effects of Shh on the transition from VZ progenitors to IPCs and activation of proliferation of the IPCs in the cortex during late gestational stages.

Research Highlights ► Shh enhances the transition from VZ progenitors to IPCs during cortical neurogenesis. ► Ptch1 is required in VZ progenitors for their self-renewal capacity. ► Cortical VZ progenitors are competent to response to Shh signal at late gestation. ► Shh and Ptch1 determine proper neural cell number and identity during neurogenesis.
Keyword Differentiation
Neural progenitor cell
Neurogenesis
Proliferation
Sonic hedgehog
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 20 October 2010

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
Institute for Molecular Bioscience - Publications
 
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Created: Mon, 07 Feb 2011, 12:09:02 EST by Susan Allen on behalf of Institute for Molecular Bioscience