AP-2α and AP-2β cooperatively function in the craniofacial surface ectoderm to regulate chromatin and gene expression dynamics during facial development

Eric Van Otterloo; Isaac Milanda; Hamish Pike; Jamie A Thompson; Hong Li; Kenneth L Jones; Trevor Williams

doi:10.7554/eLife.70511

Back

AP-2α and AP-2β cooperatively function in the craniofacial surface ectoderm to regulate chromatin and gene expression dynamics during facial development

Journal article

Open access

Peer reviewed

AP-2α and AP-2β cooperatively function in the craniofacial surface ectoderm to regulate chromatin and gene expression dynamics during facial development

Eric Van Otterloo, Isaac Milanda, Hamish Pike, Jamie A Thompson, Hong Li, Kenneth L Jones and Trevor Williams

eLife, Vol.11, e70511

03/25/2022

DOI: 10.7554/eLife.70511

PMCID: PMC9038197

PMID: 35333176

Files and links (1)

url

https://doi.org/10.7554/eLife.70511View

Published (Version of record) Open Access

Abstract

The facial surface ectoderm is essential for normal development of the underlying cranial neural crest cell populations, providing signals that direct appropriate growth, patterning, and morphogenesis. Despite the importance of the ectoderm as a signaling center, the molecular cues and genetic programs implemented within this tissue are understudied. Here, we show that removal of two members of the AP-2 transcription factor family, AP-2α and AP-2ß, within the early embryonic ectoderm of the mouse leads to major alterations in the craniofacial complex. Significantly, there are clefts in both the upper face and mandible, accompanied by fusion of the upper and lower jaws in the hinge region. Comparison of ATAC-seq and RNA-seq analyses between controls and mutants revealed significant changes in chromatin accessibility and gene expression centered on multiple AP-2 binding motifs associated with enhancer elements within these ectodermal lineages. In particular, loss of these AP-2 proteins affects both skin differentiation as well as multiple signaling pathways, most notably the WNT pathway. We also determined that the mutant clefting phenotypes that correlated with reduced WNT signaling could be rescued by ligand overexpression in the ectoderm. Collectively, these findings highlight a conserved ancestral function for AP-2 transcription factors in ectodermal development and signaling, and provide a framework from which to understand the gene regulatory network operating within this tissue that directs vertebrate craniofacial development.

Gene Expression

Animals

Chromatin

Ectoderm - metabolism

Mice

Transcription Factor AP-2 - genetics

Transcription Factor AP-2 - metabolism

Transcription Factors - genetics

Details

Title: Subtitle: AP-2α and AP-2β cooperatively function in the craniofacial surface ectoderm to regulate chromatin and gene expression dynamics during facial development
Creators: Eric Van Otterloo - University of Colorado Anschutz Medical Campus
Isaac Milanda - University of Colorado Anschutz Medical Campus
Hamish Pike - University of Colorado Anschutz Medical Campus
Jamie A Thompson - University of Iowa
Hong Li - University of Colorado Anschutz Medical Campus
Kenneth L Jones - University of Colorado Anschutz Medical Campus
Trevor Williams - University of Colorado Anschutz Medical Campus
Resource Type: Journal article
Publication Details: eLife, Vol.11, e70511
DOI: 10.7554/eLife.70511
PMID: 35333176
PMCID: PMC9038197
NLM abbreviation: Elife
ISSN: 2050-084X
eISSN: 2050-084X
Grant note: R01 DE012728 / NIDCR NIH HHS 2R01 DE12728 / NIDCR NIH HHS
Language: English
Date published: 03/25/2022
Academic Unit: Anatomy and Cell Biology; Craniofacial Anomalies Research Center; Dental Research; Periodontics
Record Identifier: 9984284351702771

Metrics

13 Record Views

26 Times Cited - Web of Science

See more details