PUBLICATION

Involvement of homeobox transcription factor Mohawk in palatogenesis

Authors
Adachi, Y., Higuchi, A., Wakai, E., Shiromizu, T., Koiwa, J., Nishimura, Y.
ID
ZDB-PUB-211129-11
Date
2021
Source
Congenital anomalies   62(1): 27-37 (Journal)
Registered Authors
Nishimura, Yuhei
Keywords
Mohawk homeobox, Sonic hedgehog, TGFβ, cleft palate, zebrafish
MeSH Terms
  • Animals
  • Cleft Palate*/chemically induced
  • Cleft Palate*/genetics
  • Gene Expression Regulation, Developmental
  • Genes, Homeobox
  • Hedgehog Proteins/genetics
  • Homeodomain Proteins*/genetics
  • Homeodomain Proteins*/metabolism
  • Mice
  • Neural Crest/growth & development
  • Palate/growth & development*
  • Transcription Factors*/genetics
  • Transcription Factors*/metabolism
  • Zebrafish/genetics
  • Zebrafish/metabolism
PubMed
34816492 Full text @ Congenit. Anom. (Kyoto)
Abstract
Palatogenesis is affected by many factors, including gene polymorphisms and exposure to toxic chemicals during sensitive developmental periods. Cleft palate is one of the most common congenital anomalies, and ongoing efforts to elucidate the molecular mechanisms underlying palatogenesis is providing useful insights to reduce the risk of this disorder. To identify novel potential regulators of palatogenesis, we analyzed public transcriptome datasets from a mouse model of cleft palate caused by selective deletion of transforming growth factor-β (TGFβ) receptor type 2 in cranial neural crest cells. We identified the homeobox transcription factor Mohawk (Mkx) as a gene downregulated in the maxilla of TGFβ knockout mice compared with wild-type mice. To examine the role of mkx in palatogenesis, we used CRISPR/Cas9 editing to generate zebrafish with impaired expression of mkxa and mkxb, the zebrafish homologs of Mkx. We found that mkx crispants expressed reduced levels of gli1, a critical transcription factor in the Sonic hedgehog (SHH) signaling pathway that plays an important role in the regulation of palatogenesis. Furthermore, we found that mkxa-/- zebrafish were more susceptible than mkxa+/+ zebrafish to the deleterious effects of cyclopamine, an inhibitor of SHH signaling, on upper jaw development. These results suggest that MKX may be involved in palatogenesis regulated by TGFβ and SHH signaling, and that impairment in MKX function may be related to the etiology of cleft palate.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping