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Development ePress online publication date 11 Aug 2004
doi: 10.1242/dev.01291
Research article
Endothelin-A receptor-dependent and -independent signaling pathways in establishing mandibular identity
Louis-Bruno Ruest,
Xilin Xiang,
Kim-Chew Lim,
Giovanni Levi,
and
David E. Clouthier*
* Author for correspondence (e-mail: clouthier{at}louisville.edu)
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.
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© The Company of Biologists Ltd 2004
