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Gremlin -mediated BMP antagonism induces the epithelial-mesenchymal feedback signaling controlling metanephric kidney and limb organogenesis
Open accessAbstract
Epithelial-mesenchymal feedback signaling is the key to diverse organogenetic processes such as limb bud development and branching morphogenesis in kidney and lung rudiments. This study establishes that the BMP antagonist gremlin (Grem1) is essential to initiate these epithelial-mesenchymal signaling interactions during limb and metanephric kidney organogenesis. A Grem1 null mutation in the mouse generated by gene targeting causes neonatal lethality because of the lack of kidneys and lung septation defects. In early limb buds, mesenchymal Grem1 is required to establish a functional apical ectodermal ridge and the epithelial-mesenchymal feedback signaling that propagates the sonic hedgehog morphogen. Furthermore, Grem1-mediated BMP antagonism is essential to induce metanephric kidney development as initiation of ureter growth,branching and establishment of RET/GDNF feedback signaling are disrupted in Grem1-deficient embryos. As a consequence, the metanephric mesenchyme is eliminated by apoptosis, in the same way as the core mesenchymal cells of the limb bud.
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Citations
Cites
Fgf8 signalling from the AER is essential for normal limb development
Lewandoski, M., Sun, X., & Martin, G. R. (2000) · Nature Genetics · doi:10.1038/82609 · Cited by 451
Cited by
Wagner, W., Wein, F., Seckinger, A., Frankhauser, M., Wirkner, U., Krause, U., Blake, J., Schwager, C., Eckstein, V., Ansorge, W., et al. (2005) · Experimental Hematology · doi:10.1016/j.exphem.2005.07.003 · Cited by 1,259
Long-Range Control of Gene Expression: Emerging Mechanisms and Disruption in Disease
Kleinjan, D. A., & van Heyningen, V. (2005) · The American Journal of Human Genetics · doi:10.1086/426833 · Cited by 873
Bone morphogenetic proteins: a critical review
Bragdon, B., Moseychuk, O., Saldanha, S., King, D., Julian, J., & Nohe, A. (2011) · Cellular Signalling · doi:10.1016/j.cellsig.2010.10.003 · Cited by 691
Regulation of early lung morphogenesis: questions, facts and controversies
Cardoso, W. V., & Lü, J. (2006) · Development · doi:10.1242/dev.02310 · Cited by 585
Bone morphogenetic proteins and their antagonists
Gazzerro, E., & Canalis, E. (2007) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-006-9000-6 · Cited by 338
Metadata
- Authors
- Michos, O., Panman, L., Vintersten, K., Beier, K., Zeller, R., & Zuniga, A.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2004-07-15
- Volume
- 131
- Issue
- 14
- Pages
- 3401-3410
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2076087769
- Cited by
- 369
- References
- 1
- FWCI
- 6.89
- Type
- journal article
- Language
- en
- Open access
- bronze
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