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)
Citation
Adachi, Y., Higuchi, A., Wakai, E., Shiromizu, T., Koiwa, J., Nishimura, Y. (2021) Involvement of homeobox transcription factor Mohawk in palatogenesis. Congenital anomalies. 62(1):27-37.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping