Roles of ADAM13-regulated Wnt activity in early Xenopus eye development.
Pericellular proteolysis by ADAM family metalloproteinases has been widely implicated in cell signaling and development. We recently found that Xenopus ADAM13, an ADAM metalloproteinase, is required for activation of canonical Wnt signaling during cranial neural crest (CNC) induction by regulating a novel crosstalk between Wnt and ephrin B (EfnB) signaling pathways (Wei et al., 2010b). In the present study we show that the metalloproteinase activity of ADAM13 also plays important roles in eye development in Xenopus tropicalis. Knockdown of ADAM13 results in reduced expression of eye field markers pax6 and rx1, as well as that of the pan-neural marker sox2. Activation of canonical Wnt signaling or inhibition of forward EfnB signaling rescues the eye defects caused by loss of ADAM13, suggesting that ADAM13 functions through regulation of the EfnB-Wnt pathway interaction. Downstream of Wnt, the head inducer Cerberus was identified as an effector that mediates ADAM13 function in early eye field formation. Furthermore, ectopic expression of the Wnt target gene snail2 restores cerberus expression and rescues the eye defects caused by ADAM13 knockdown. Together these data suggest an important role of ADAM13-regulated Wnt activity in eye development in Xenopus.
Department of Cell Biology and the Morphogenesis and Regenerative Medicine Institute, University of Virginia Health System, Charlottesville, VA 22908, USA. Shuo.Wei@mail.wvu.edu
Shuo
S
Wei
Guofeng
G
Xu
Lance C
LC
Bridges
Phoebe
P
Williams
Takuya
T
Nakayama
Anoop
A
Shah
Robert M
RM
Grainger
Judith M
JM
White
Douglas W
DW
DeSimone
D000818:Animals; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D036387:Ephrin-B1 / Q000235:genetics; D005123:Eye / Q000196:embryology / Q000378:metabolism*; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000235:genetics; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics; D060449:Wnt Signaling Pathway; D014981:Xenopus / Q000196:embryology / Q000235:genetics*; D029867:Xenopus Proteins / Q000235:genetics* / Q000502:physiology
D036387:Ephrin-B1; D005136:Eye Proteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; C561115:SNAI2 protein, Xenopus; D014157:Transcription Factors; D051153:Wnt Proteins; D029867:Xenopus Proteins; C100866:cer1 protein, Xenopus