|Presenting Author(s)||Caroline Dealy|
|Abstract Title||Roles for EGFR signaling in vertebrate limb patterning, cell death, and endochondral bone formation.|
|Full author List||Minoru Omi, Nita J. Maihle*, Melanie Fisher, and Caroline N. Dealy|
|Text of abstract||
The Epidermal Growth Factor receptor (EGFR) signaling network is a crucial regulator of wing and leg development in Drosophila, but its role in vertebrate limb morphogenesis has received little attention. The EGFR, also known as ErbB1, is a tyrosine kinase receptor belonging to the vertebrate ErbB family. To study the functions of ErbB1 signaling in the vertebrate limb, we expressed a constitutively active ErbB1 receptor in the limb buds of developing chick embryos in ovo using an RCAS-retroviral vector. Expression of activated ErbB1 during limb patterning stages causes pre- and post-axial polydactyly, including mirror-image type digit duplication, as well as syndactyly. These phenotypes are accompanied by ectopic anterior expression of Sonic hedgehog, formation of ectopic and/or extended FGF-8 expressing AERs, and inhibition of interdigital cell death. In addition, ectopic dorsal scales are present on the ventral autopod surface of the limb, indicating the limb is dorsalized. These results indicate roles for EGFR-mediated signaling pathways in AP and DV patterning, AER induction, and cell survival during limb patterning. We also found that expression of activated ErbB1 during later stages of limb development alters the subsequent differentiation of the skeletal elements. Our results suggest EGFR signaling is involved in the regulation of chondrocyte maturation and osteoblast differentiation during endochondral bone formation.
Together, these studies implicate the EGFR/ErbB signaling network as a potential key signaling pathway regulating vertebrate limb development.
|Which session is your work most relevant to:||Limb patterning|
© Copyright 2003 The Medical Research Council Human Genetics Unit
All Rights Reserved