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

Joshua W. Vincentz, Jose J. Casasnovas, Ralston M. Barnes, Jianwen Que, David E. Clouthier, Jun Wang, Anthony Firulli

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)7563-7568
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number27
DOIs
StatePublished - Jul 5 2016

Fingerprint

Neural Crest
Branchial Region
Bone and Bones
Transcription Factors
Homeodomain Proteins
Neural Tube
Proteins
Homeobox Genes
Incisor
Jaw
Mandible
Reporter Genes
Connective Tissue
Cues
Embryonic Structures
Gene Expression

Keywords

  • Bmp
  • Cranial neural crest cells
  • Development
  • DLX
  • HAND1

ASJC Scopus subject areas

  • General

Cite this

Exclusion of Dlx5/6 expression from the distal-most mandibular arches enables BMP-mediated specification of the distal cap. / Vincentz, Joshua W.; Casasnovas, Jose J.; Barnes, Ralston M.; Que, Jianwen; Clouthier, David E.; Wang, Jun; Firulli, Anthony.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 113, No. 27, 05.07.2016, p. 7563-7568.

Research output: Contribution to journalArticle

Vincentz, Joshua W. ; Casasnovas, Jose J. ; Barnes, Ralston M. ; Que, Jianwen ; Clouthier, David E. ; Wang, Jun ; Firulli, Anthony. / Exclusion of Dlx5/6 expression from the distal-most mandibular arches enables BMP-mediated specification of the distal cap. In: Proceedings of the National Academy of Sciences of the United States of America. 2016 ; Vol. 113, No. 27. pp. 7563-7568.
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