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First published online 11 August 2004
doi: 10.1242/dev.01291
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1 Department of Molecular, Cellular and Craniofacial Biology and the Birth
Defects Center, University of Louisville, Louisville, KY 40292, USA
2 Department of Cell and Developmental Biology, University of Michigan Medical
School, Ann Arbor, MI 48109, USA
3 UMR5166 CNRS/MNHN Evolution des Régulations Endocriniennes, 7 rue
Cuvier, 75005 Paris, France
* Author for correspondence (e-mail: clouthier{at}louisville.edu)
Accepted 7 June 2004
The lower jaw skeleton is derived from cephalic neural crest (CNC) cells that reside in the mandibular region of the first pharyngeal arch. Endothelin-A receptor (Ednra) signaling in crest cells is crucial for their development, as Ednra–/– mice are born with severe craniofacial defects resulting in neonatal lethality. In this study, we undertook a more detailed analysis of mandibular arch development in Ednra–/– embryos to better understand the cellular and molecular basis for these defects. We show that most lower jaw structures in Ednra–/– embryos undergo a homeotic transformation into maxillary-like structures similar to those observed in Dlx5/Dlx6–/– embryos, though lower incisors are still present in both mutant embryos. These structural changes are preceded by aberrant expansion of proximal first arch gene expression into the distal arch, in addition to the previously described loss of a Dlx6/Hand2 expression network. However, a small distal Hand2 expression domain remains. Although this distal expression is not dependent on either Ednra or Dlx5/Dlx6 function, it may require one or more GATA factors. Using fate analysis, we show that these distal Hand2-positive cells probably contribute to lower incisor formation. Together, our results suggest that the establishment of a `mandibular identity' during lower jaw development requires both Ednra-dependent and -independent signaling pathways.
Key words: Mouse, Bone, Mandible, Patterning, Neural crest cell, Homeobox gene
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