Cell lineage- and expression-based inference of the roles of forkhead box transcription factor Foxc2 in craniofacial development

Manami Takenoshita, Masaki Takechi, Tri Vu Hoang, Toshiko Furutera, Chisaki Akagawa, Worachat Namangkalakul, Kazushi Aoto, Tsutomu Kume, Michiyo Miyashin, Tsutomu Iwamoto, Sachiko Iseki*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background: Foxc2 is a member of the winged helix/forkhead (Fox) box family of transcription factors. Loss of function of Foxc2 causes craniofacial abnormalities such as cleft palate and deformed cranial base, but its role during craniofacial development remains to be elucidated. Results: The contributions of Foxc2-positive and its descendant cells to the craniofacial structure at E18.5 were examined using a tamoxifen-inducible Cre driver mouse (Foxc2-CreERT2) crossed with the R26R-LacZ reporter mouse. Foxc2 expression at E8.5 is restricted to the cranial mesenchyme, contributing to specific components including the cranial base, sensory capsule, tongue, upper incisor, and middle ear. Expression at E10.5 was still positively regulated in most of those regions. In situ hybridization analysis of Foxc2 and its closely related gene, Foxc1, revealed that expression domains of these genes largely overlap in the cephalic mesenchyme. Meanwhile, the tongue expressed Foxc2 but not Foxc1, and its development was affected by the neural crest-specific deletion of Foxc2 in mice (Wnt1-Cre; Foxc2fl/fl). Conclusions: Foxc2 is expressed in cranial mesenchyme that contributes to specific craniofacial tissue components from an early stage, and it seems to be involved in their development in cooperation with Foxc1. Foxc2 also has its own role in tongue development.

Original languageEnglish (US)
Pages (from-to)1125-1139
Number of pages15
JournalDevelopmental Dynamics
Volume250
Issue number8
DOIs
StatePublished - Aug 2021

Keywords

  • Foxc1
  • Foxc2
  • cranial base
  • sensory capsule
  • tongue

ASJC Scopus subject areas

  • Developmental Biology

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