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Rescuing craniofacial development in an avian model of holoprosencephaly
Author(s) -
Chong H. Jonathan,
Marcucio Ralph
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.472.1
Subject(s) - ectoderm , holoprosencephaly , forebrain , sonic hedgehog , craniofacial , biology , microbiology and biotechnology , hedgehog signaling pathway , smoothened , signal transduction , anatomy , neuroscience , embryogenesis , genetics , embryo , central nervous system , pregnancy , fetus
Blockade of Sonic hedgehog (Shh) signaling in the embryonic forebrain leads to altered gene expression in the facial ectoderm and morphologic changes resembling holoprosencephaly. However, the molecular pathways that are involved in communications between the forebrain and facial ectoderm are not known. The aim of this study was to test the ability of candidate pathways to restore ectodermal gene expression and craniofacial morphology following blockade of forebrain Shh signaling. Activation of the Bone Morphogenetic Protein‐2 (BMP‐2) pathway in the head mesenchyme of treated embryos did not rescue morphology and created severe phenotypes. In contrast, preliminary results suggest that activation of the Shh pathway leads to partial morphologic rescue. Ongoing studies are examining changes in gene expression patterns in the ectoderm covering the upper jaw anlagen. These data suggest that exogenous Shh signaling, but not BMP‐2 signaling, restores forebrain‐ectodermal communications and will help elucidate the normal signaling mechanisms between these tissues. Grant Funding Source NIH/NIDCR R01DE018234 to R.M. and HHMI Medical Research Training Fellowship to H.J.C.