Craniofacial anomalies of the cultured mouse embryo induced by inhibition of sonic hedgehog signaling: An animal model of holoprosencephaly

Takashi Nagase, Miki Nagase, Noriko Osumi, Satoru Fukuda, Shun Nakamura, Kanae Ohsaki, Kiyonori Harii, Hirotaka Asato, Kotaro Yoshimura

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

The pathogenesis of holoprosencephaly is multifactorial, and blockage of Sonic hedgehog signaling is one of the most important causative factors in animal models and human cases. In this study, the authors analyzed facial anomalies of mouse embryos, which were cultured in vitro and exposed to cyclopamine, an alkaloid blocker of Sonic hedgehog signaling. When cultured with cyclopamine for embryonic day 8.5 to 10.5, the whole body size was smaller than normal, and the distance and angle between the nasal placodes were remarkably reduced. Extension of the cranial surface vessels also was noted. No cyclopia was observed. Migration of the cranial neural crest cells seemed to be intact. Expressions of Patched-1 and Gli-1, downstream genes of Sonic hedgehog signaling, also were down-regulated in in situ hybridization and real-time reverse transcriptase-polymerase chain reaction analyses. The authors consider that these facial anomalies represent milder phenotypes of holoprosencephaly.

Original languageEnglish
Pages (from-to)80-88
Number of pages9
JournalJournal of Craniofacial Surgery
Volume16
Issue number1
DOIs
Publication statusPublished - 2005 Jan

Keywords

  • Holoprosencephaly
  • Mouse embryo
  • Neural crest cells
  • Sonic hedgehog
  • Whole embryo culture

ASJC Scopus subject areas

  • Surgery
  • Otorhinolaryngology

Fingerprint Dive into the research topics of 'Craniofacial anomalies of the cultured mouse embryo induced by inhibition of sonic hedgehog signaling: An animal model of holoprosencephaly'. Together they form a unique fingerprint.

Cite this