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Proc Natl Acad Sci U S A. 2016 Jul 5;113(27):7563-8. doi: 10.1073/pnas.1603930113. Epub 2016 Jun 22.

Exclusion of Dlx5/6 expression from the distal-most mandibular arches enables BMP-mediated specification of the distal cap.

Author information

1
Riley Heart Research Center, Herman B. Wells Center for Pediatric Research Division of Pediatric Cardiology, Departments of Anatomy, Biochemistry, and Medical and Molecular Genetics, Indiana University Medical School, Indianapolis, IN 46202;
2
Biologics Discovery California, Bristol-Myers Squibb, Redwood City, CA 94063;
3
Department of Medicine, Columbia University Medical Center, New York, NY 10032;
4
Department of Craniofacial Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80108;
5
Department of Molecular Physiology and Biophysics, Texas Heart Institute, Baylor College of Medicine, Houston, TX 77030.
6
Riley Heart Research Center, Herman B. Wells Center for Pediatric Research Division of Pediatric Cardiology, Departments of Anatomy, Biochemistry, and Medical and Molecular Genetics, Indiana University Medical School, Indianapolis, IN 46202; tfirulli@iu.edu.

Abstract

Cranial neural crest cells (crNCCs) migrate from the neural tube to the pharyngeal arches (PAs) of the developing embryo and, subsequently, differentiate into bone and connective tissue to form the mandible. Within the PAs, crNCCs respond to local signaling cues to partition into the proximo-distally oriented subdomains that convey positional information to these developing tissues. Here, we show that the distal-most of these subdomains, the distal cap, is marked by expression of the transcription factor Hand1 (H1) and gives rise to the ectomesenchymal derivatives of the lower incisors. We uncover a H1 enhancer sufficient to drive reporter gene expression within the crNCCs of the distal cap. We show that bone morphogenic protein (BMP) signaling and the transcription factor HAND2 (H2) synergistically regulate H1 distal cap expression. Furthermore, the homeodomain proteins distal-less homeobox 5 (DLX5) and DLX6 reciprocally inhibit BMP/H2-mediated H1 enhancer regulation. These findings provide insights into how multiple signaling pathways direct transcriptional outcomes that pattern the developing jaw.

KEYWORDS:

Bmp; DLX; HAND1; cranial neural crest cells; development

PMID:
27335460
PMCID:
PMC4941460
DOI:
10.1073/pnas.1603930113
[Indexed for MEDLINE]
Free PMC Article

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