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Publication : Antagonistic crosstalk of Wnt/beta-catenin/Bmp signaling within the Apical Ectodermal Ridge (AER) regulates interdigit formation.

First Author  Villacorte M Year  2010
Journal  Biochem Biophys Res Commun Volume  391
Issue  4 Pages  1653-7
PubMed ID  20043884 Mgi Jnum  J:157085
Mgi Id  MGI:4430000 Doi  10.1016/j.bbrc.2009.12.109
Citation  Villacorte M, et al. (2010) Antagonistic crosstalk of Wnt/beta-catenin/Bmp signaling within the Apical Ectodermal Ridge (AER) regulates interdigit formation. Biochem Biophys Res Commun 391(4):1653-7
abstractText  Digit and interdigit (D/ID) development is one of the important research fields in molecular developmental biology. Interdigital cell death (ICD) is a morphogenetic event which has been considered as an essential process for D/ID formation. Although some growth factors including Bmp and Fgf signaling can modulate ICD, growth factor crosstalk regulating ICD is poorly understood. Wnt canonical pathway and Bmp signal crosstalk has been considered as the essential growth factor crosstalk in organogenesis. To elucidate the crosstalk to regulate the D/ID formation, we analyzed conditional mutant mice with limb bud ectoderm expressing constitutively activated beta-catenin signaling. We showed that modulation of Wnt/beta-catenin signal in the limb ectoderm including the AER regulates ID apoptosis. We also demonstrated that Wnt/beta-catenin signaling in the ectoderm can positively regulate Fgf8 possibly antagonizing the epithelial derived Bmp signaling. Human birth defects for digit abnormalities have been known to be affected by multiple parameters. Elucidation of the potential mechanisms underlying such D/ID development is an urgent medical issue to be solved. This work would be one of the first studies showing essential growth factor cascades in the D/ID formation.
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