Antagonistic crosstalk of Wnt/beta-catenin/Bmp signaling within the Apical Ectodermal Ridge (AER) regulates interdigit formation.
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.
Villacorte
Mylah
M
Department of Organ Formation, Institute of Molecular Embryology and Genetics, Kumamoto University, Honjo 2-2-1, Kumamoto 860-0811, Japan.
Suzuki
Kentaro
K
Hayashi
Katsuhiko
K
de Sousa Lopes
Susana Chuva
SC
Haraguchi
Ryuma
R
Taketo
Makoto M
MM
Nakagata
Naomi
N
Yamada
Gen
G
D000818:Animals; D017209:Apoptosis; D015415:Biomarkers; D052004:Bone Morphogenetic Protein Receptors / Q000378:metabolism*; D004475:Ectoderm / Q000002:abnormalities / Q000196:embryology* / Q000378:metabolism; D051524:Fibroblast Growth Factor 8 / Q000235:genetics / Q000378:metabolism; D018878:Limb Buds / Q000002:abnormalities / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
D015415:Biomarkers; C496457:Fgf8 protein, mouse; D051153:Wnt Proteins; D051176:beta Catenin; D051524:Fibroblast Growth Factor 8; D052004:Bone Morphogenetic Protein Receptors