Journal article
TFAP2 paralogs regulate midfacial development in part through a conserved ALX genetic pathway
Development (Cambridge), Vol.151(1), dev202095
01/01/2024
DOI: 10.1242/dev.202095
PMCID: PMC10820886
PMID: 38063857
Appears in UI Libraries Support Open Access
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.
Details
- Title: Subtitle
- TFAP2 paralogs regulate midfacial development in part through a conserved ALX genetic pathway
- Creators
- Timothy T Nguyen - Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, IA 52242, USAJennyfer M Mitchell - University of Colorado Anschutz Medical CampusMichaela D Kiel - University of IowaColin P Kenny - Department of Surgery, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAHong Li - University of Colorado Anschutz Medical CampusKenneth L Jones - University of Colorado Anschutz Medical CampusRobert A Cornell - University of WashingtonTrevor J Williams - University of Colorado Anschutz Medical CampusJames T Nichols - University of Colorado Anschutz Medical CampusEric Van Otterloo - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Development (Cambridge), Vol.151(1), dev202095
- DOI
- 10.1242/dev.202095
- PMID
- 38063857
- PMCID
- PMC10820886
- NLM abbreviation
- Development
- eISSN
- 1477-9129
- Publisher
- The Company of Biologists
- Grant note
- DOI: 10.13039/100000072, name: National Institute for Dental and Craniofacial Research, award: F31DE032881, R00DE026823, R01DE030448, R01DE029193, 2R01DE012728, F32DE029995, T90DE023520; DOI: 10.13039/100008893, name: University of Iowa; DOI: 10.13039/100000069, name: National Institute of Arthritis and Musculoskeletal and Skin Diseases, award: R01AR062547; name: University of Iowa College of Dentistry
- Language
- English
- Electronic publication date
- 12/08/2023
- Date published
- 01/01/2024
- Academic Unit
- Anatomy and Cell Biology; Surgery; Craniofacial Anomalies Research Center; Dental Research; Periodontics
- Record Identifier
- 9984530398602771
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