Ptch1-mediated dosage-dependent action of Shh signaling regulates neural progenitor development at late gestational stages.
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.
Shikata
Yayoi
Y
Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Okada
Toshiaki
T
Hashimoto
Mitsuhiro
M
Ellis
Tammy
T
Matsumaru
Daisuke
D
Shiroishi
Toshihiko
T
Ogawa
Masaharu
M
Wainwright
Brandon
B
Motoyama
Jun
J
D000818:Animals; D001921:Brain / Q000196:embryology*; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D018274:Electroporation; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D006652:Histological Techniques; D051379:Mice; D016296:Mutagenesis; D055495:Neurogenesis / Q000502:physiology*; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology*
D053823:Hedgehog Proteins; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; C000606240:Ptch1 protein, mouse; D011956:Receptors, Cell Surface