Abstract:
:Mutations in the Bone Morphogenetic Protein (BMP) pathway are associated with a range of defects in skeletal formation. Genetic analysis of BMP signaling requirements is complicated by the presence of three partially redundant BMPs that are required for multiple stages of limb development. We generated an inducible allele of a BMP inhibitor, Gremlin, which reduces BMP signaling. We show that BMPs act in a dose and time dependent manner in which early reduction of BMPs result in digit loss, while inhibiting overall BMP signaling between E10.5 and E11.5 allows polydactylous digit formation. During this period, inhibiting BMPs extends the duration of FGF signaling. Sox9 is initially expressed in normal digit ray domains but at reduced levels that correlate with the reduction in BMP signaling. The persistence of elevated FGF signaling likely promotes cell proliferation and survival, inhibiting the activation of Sox9 and secondarily, inhibiting the differentiation of Sox9-expressing chondrocytes. Our results provide new insights into the timing and clarify the mechanisms underlying BMP signaling during digit morphogenesis.
journal_name
Dev Bioljournal_title
Developmental biologyauthors
Norrie JL,Lewandowski JP,Bouldin CM,Amarnath S,Li Q,Vokes MS,Ehrlich LIR,Harfe BD,Vokes SAdoi
10.1016/j.ydbio.2014.07.003subject
Has Abstractpub_date
2014-09-15 00:00:00pages
270-281issue
2eissn
0012-1606issn
1095-564Xpii
S0012-1606(14)00337-6journal_volume
393pub_type
杂志文章abstract::It has been suggested that the mesonephros has a role in normal limb development. This hypothesis was directly tested by removing the mesonephros adjacent to the presumptive limb region of stage 12-18 chick embryos using microsurgery or laser ablation. The experimental manipulation resulted in reduced limb outgrowth o...
journal_title:Developmental biology
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journal_title:Developmental biology
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journal_title:Developmental biology
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pub_type: 杂志文章,评审
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journal_title:Developmental biology
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journal_title:Developmental biology
pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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