Endogenous bone morphogenetic proteins regulate outgrowth and epithelial survival during avian lip fusion
Author:
Ashique Amir M.1, Fu Katherine2, Richman Joy M.1
Affiliation:
1. Present address: The Forsyth Institute, Harvard School of Dental Medicine, 140 Fenway Avenue, Boston, MA, USA 2. Department of Oral Health Sciences, Faculty of Dentistry, The University of British Columbia, Vancouver BC, Canada
Abstract
Our expression studies of bone morphogenetic proteins (BMPs) and Noggin (a BMP antagonist) in the embryonic chicken face suggested that BMP signals were important for closure of the upper lip or primary palate. We noted that Noggin expression was restricted to the frontonasal mass epithelium but was reduced at the corners of the frontonasal mass (globular processes) just prior to fusion with the adjacent maxillary prominences. We therefore performed gain- and loss-of-function experiments to determine the role of BMPs in lip formation. Noggin treatment led to reduced proliferation and outgrowth of the frontonasal mass and maxillary prominences and ultimately to the deletion of the maxillary and palatine bones. The temporary block in BMP signalling in the mesenchyme also promoted epithelial survival. Noggin treatment also upregulated expression of endogenous BMPs, therefore we investigated whether increasing BMP levels would lead to the same phenotype. A BMP2 bead was implanted into the globular process and a similar phenotype to that produced by Noggin resulted. However, instead of a decrease in proliferation, defects were caused by increased programmed cell death, first in the epithelium and then in the mesenchyme. Programmed cell death was induced primarily in the lateral frontonasal mass with very little cell death medial to the bead. The asymmetric cell death pattern was correlated with a rapid induction of Noggin in the same embryos, with transcripts complementary to the regions with increased cell death. We have demonstrated a requirement for endogenous BMP in the proliferation of facial mesenchyme and that mesenchymal signals promote either survival or thinning of the epithelium. We furthermore demonstrated in vivo that BMP homeostasis is regulated by increasing expression of ligand or antagonist and that such mechanisms may help to protect the embryo from changes in growth factor levels during development or after exposure to teratogens.
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
Reference81 articles.
1. Ahlgren, S. C. and Bronner-Fraser, M. (1999). Inhibition of sonic hedgehog signaling in vivo results in craniofacial neural crest cell death. Curr. Biol.9, 1304-1314. 2. Ashique, A. M., Fu, K. and Richman, J. M. (2002). Signalling via type IA and type IB bone morphogenetic protein receptors (BMPR) regulates intramembranous bone formation, chondrogenesis and feather formation in the chicken embryo. Int. J. Dev. Biol.46, 243-253. 3. Bachiller, D., Klingensmith, J., Kemp, C., Belo, J. A., Anderson, R. M., May, S. R., McMahon, J. A., McMahon, A. P., Harland, R. M., Rossant, J. et al. (
2000). The organizer factors Chordin and Noggin are required for mouse forebrain development. Nature403, 658-661. 4. Bardot, B., Lecoin, L., Huillard, E., Calothy, G. and Marx, M. (2001). Expression pattern of the drm/gremlin gene during chicken embryonic development. Mech. Dev.101, 263-265. 5. Barlow, A. J. and Francis-West, P. H. (1997). Ectopic application of recombinant BMP-2 and BMP-4 can change patterning of developing chick facial primordia. Development124, 391-398.
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