Wnt signaling mediates regional specification in the vertebrate face.
At early stages of development, the faces of vertebrate embryos look remarkably similar, yet within a very short timeframe they adopt species-specific facial characteristics. What are the mechanisms underlying this regional specification of the vertebrate face? Using transgenic Wnt reporter embryos we found a highly conserved pattern of Wnt responsiveness in the developing mouse face that later corresponded to derivatives of the frontonasal and maxillary prominences. We explored the consequences of disrupting Wnt signaling, first using a genetic approach. Mice carrying compound null mutations in the nuclear mediators Lef1 and Tcf4 exhibited radically altered facial features that culminated in a hyperteloric appearance and a foreshortened midface. We also used a biochemical approach to perturb Wnt signaling and found that in utero delivery of a Wnt antagonist, Dkk1, produced similar midfacial malformations. We tested the hypothesis that Wnt signaling is an evolutionarily conserved mechanism controlling facial morphogenesis by determining the pattern of Wnt responsiveness in avian faces, and then by evaluating the consequences of Wnt inhibition in the chick face. Collectively, these data elucidate a new role for Wnt signaling in regional specification of the vertebrate face, and suggest possible mechanisms whereby species-specific facial features are generated.
Brugmann
Samantha A
SA
Department of Plastic and Reconstructive Surgery, Stanford University, Stanford, CA 94305, USA.
Goodnough
L Henry
LH
Gregorieff
Alex
A
Leucht
Philipp
P
ten Berge
Derk
D
Fuerer
Christophe
C
Clevers
Hans
H
Nusse
Roel
R
Helms
Jill A
JA
D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D005145:Face / Q000002:abnormalities* / Q000196:embryology*; D017930:Genes, Reporter; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics; D008445:Maxillofacial Development / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D015398:Signal Transduction; D051820:TCF Transcription Factors / Q000235:genetics; D000073940:Transcription Factor 4; D051153:Wnt Proteins / Q000235:genetics / Q000502:physiology*
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D009419:Nerve Tissue Proteins; D051820:TCF Transcription Factors; C090743:Tcf4 protein, mouse; D000073940:Transcription Factor 4; D051153:Wnt Proteins