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Studies on epidermal growth factor receptor signaling in vertebrate limb patterning
Author(s) -
Omi Minoru,
Fisher Melanie,
Maihle Nita J.,
Dealy Caroline N.
Publication year - 2005
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.20353
Subject(s) - biology , limb development , apical ectodermal ridge , sonic hedgehog , ectopic expression , fgf8 , gli3 , microbiology and biotechnology , bone morphogenetic protein , bone morphogenetic protein 4 , zone of polarizing activity , morphogenesis , patched , mesoderm , limb bud , cyclopamine , signal transduction , anatomy , hedgehog , fibroblast growth factor , ectoderm , transcription factor , receptor , genetics , repressor , embryonic stem cell , gene , embryogenesis , embryo
The epidermal growth factor receptor (EGFR) regulates multiple patterning events in Drosophila limb development, but its role in vertebrate limb morphogenesis has received little attention. The EGFR and several of its ligands are expressed in developing vertebrate limbs in manners consistent with potential patterning roles. To gain insight into functions of EGFR signaling in vertebrate limb development, we expressed a constitutively active EGFR in developing chick limbs in ovo. Expression of activated EGFR causes pre‐ and postaxial polydactyly, including mirror‐image–type digit duplication, likely due to induction of ectopic expression and/or modulation of genes involved in anterior–posterior (AP) patterning such as Sonic hedgehog ( Shh ), dHand, Patched ( Ptc ), Gli3, Hoxd13, Hoxd11, bone morphogenetic protein 2 ( Bmp2 ), Gremlin , and FGF4 . Activation of EGFR signaling dorsalizes the limb and alters expression of the dorsal–ventral (DV) patterning genes Wnt7a, Lmx , and En1 . Ectopic and/or extended FGF8 expressing apical ectodermal ridges (AERs) are also seen. Interdigital regression is inhibited and the digits fail to separate, leading to syndactyly, likely due to antiapoptotic and pro‐proliferative effects of activated EGFR signaling on limb mesoderm, and/or attenuation of interdigital Bmp4 expression. These findings suggest potential roles for EGFR signaling in AP and DV patterning, AER formation, and cell survival during limb morphogenesis. Developmental Dynamics 233:288–300, 2005. © 2005 Wiley‐Liss, Inc.