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

Yayoi Shikata, Toshiaki Okada, Mitsuhiro Hashimoto, Tammy Ellis, Daisuke Matsumaru, Toshihiko Shiroishi, Masaharu Ogawa, Brandon Wainwright, Jun Motoyama

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)147-159
Number of pages13
JournalDevelopmental Biology
Volume349
Issue number2
DOIs
Publication statusPublished - 2011 Jan 15

Keywords

  • Differentiation
  • Neural progenitor cell
  • Neurogenesis
  • Proliferation
  • Sonic hedgehog

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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