PUBLICATION
TFAP2 paralogs regulate midfacial development in part through a conserved ALX genetic pathway
- Authors
- Nguyen, T.T., Mitchell, J.M., Kiel, M.D., Kenny, C.P., Li, H., Jones, K.L., Cornell, R.A., Williams, T.J., Nichols, J.T., Van Otterloo, E.
- ID
- ZDB-PUB-231209-3
- Date
- 2023
- Source
- Development (Cambridge, England) 151(1): (Journal)
- Registered Authors
- Kenny, Colin
- Keywords
- ALX, Branchio-Oculo-Facial syndrome, Char syndrome, Frontonasal Dysplasia, Neural crest, TFAP2
- Datasets
- GEO:GSE250450, GEO:GSE220081
- MeSH Terms
-
- Animals
- Cell Differentiation/genetics
- Gene Expression Regulation, Developmental
- Genes, Homeobox
- Mice
- Neural Crest
- Transcription Factor AP-2/genetics
- Transcription Factor AP-2/metabolism
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Zebrafish Proteins*/genetics
- PubMed
- 38063857 Full text @ Development
Citation
Nguyen, T.T., Mitchell, J.M., Kiel, M.D., Kenny, C.P., Li, H., Jones, K.L., Cornell, R.A., Williams, T.J., Nichols, J.T., Van Otterloo, E. (2023) TFAP2 paralogs regulate midfacial development in part through a conserved ALX genetic pathway. Development (Cambridge, England). 151(1):.
Abstract
Cranial neural crest development is governed by positional gene regulatory networks (GRNs). Fine-tuning of the GRN components underly facial shape variation, yet how those in the midface are connected and activated remain poorly understood. Here, we show that concerted inactivation of Tfap2a and Tfap2b in the murine neural crest, even during the late migratory phase, results in a midfacial cleft and skeletal abnormalities. Bulk and single-cell RNA-seq profiling reveal that loss of both Tfap2 family members dysregulates numerous midface GRN components involved in midface morphogenesis, patterning, and differentiation. Notably, Alx1/3/4 (Alx) transcript levels are reduced, while ChIP-seq analyses suggest TFAP2 directly and positively regulates Alx gene expression. TFAP2 and ALX co-expression in midfacial neural crest cells of both mouse and zebrafish implies conservation of this regulatory axis across vertebrates. Consistent with this notion, tfap2a zebrafish mutants present abnormal alx3 expression patterns, Tfap2a binds alx loci, and tfap2a-alx3 genetic interactions are observed. Together, these data demonstrate TFAP2 paralogs regulate vertebrate midfacial development in part by activating expression of ALX transcription factor genes.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping