Interdigit Bone Morphogenetic Protein signaling is essential for Programmed Cell Death and is implicated in digit formation

Wednesday, October 10, 2012 — Poster Session II
Noon – 2:00 p.m	Natcher Conference Center, Building 45	NCI	DEV-8

* FARE Award Winner

Authors

• MK Kaltcheva
• SP Underwood
• BD Harfe
• MB Lewandoski

Abstract

Shaping of the embryonic limb involves many processes including growth, differentiation, and programmed cell death (PCD). Our previous work has shown that Bone Morphogenetic Protein (BMP) signaling regulates interdigit (ID) PCD indirectly by modulating the secretion of Fibroblast Growth Factors from the apical ectodermal ridge. However, it is unclear whether ID BMPs also trigger PCD directly. To genetically test this, we inactivated the gene encoding the Bmpr1A receptor within the interdigit tissue with Osr1-Cre. The resulting mutants are syndactylous and show a decrease of ID PCD at embryonic day 13.5. To test redundancy between BMPR1A and BMPR1B in PCD we inactivated ID Bmpr1A in a Bmpr1B null/null background. This compound mutant has a further decrease in PCD and surprisingly rescues a subset of the skeletal malformations observed in Bmpr1B null/null mice: a complete rescue of the most anterior digit. To fully understand the role of ID BMP signaling on normal limb development, we are also inactivating Bmp2, 4, and 7 with Osr1-Cre. Preliminary analysis of these mutants reveals a syndactylous phenotype and an ectopic posterior skeletal element. This work will clarify the role of ID BMP signaling in directly regulating PCD and digit formation.

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