Forced activation of Wnt signaling alters morphogenesis and sensory organ identity in the chicken inner ear.
Components of the Wnt signaling pathway are expressed in the developing inner ear. To explore their role in ear patterning, we used retroviral gene transfer to force the expression of an activated form of beta-catenin that should constitutively activate targets of the canonical Wnt signaling pathway. At embryonic day 9 (E9) and beyond, morphological defects were apparent in the otic capsule and the membranous labyrinth, including ectopic and fused sensory patches. Most notably, the basilar papilla, an auditory organ, contained infected sensory patches with a vestibular phenotype. Vestibular identity was based on: (1) stereociliary bundle morphology; (2) spacing of hair cells and supporting cells; (3) the presence of otoliths; (4) immunolabeling indicative of vestibular supporting cells; and (5) expression of Msx1, a marker of certain vestibular sensory organs. Retrovirus-mediated misexpression of Wnt3a also gave rise to ectopic vestibular patches in the cochlear duct. In situ hybridization revealed that genes for three Frizzled receptors, c-Fz1, c-Fz7, and c-Fz10, are expressed in and adjacent to sensory primordia, while Wnt4 is expressed in adjacent, nonsensory regions of the cochlear duct. We hypothesize that Wnt/beta-catenin signaling specifies otic epithelium as macular and helps to define and maintain sensory/nonsensory boundaries in the cochlear duct.
Stevens
Craig B
CB
Department of Biological Sciences, Purdue University, West Lafayette, IN 47907-1392, USA.
Davies
Alex L
AL
Battista
Sarah
S
Lewis
Julian H
JH
Fekete
Donna M
DM
D000818:Animals; D019521:Body Patterning; D002642:Chick Embryo; D003053:Cochlear Duct / Q000196:embryology / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D007758:Ear, Inner / Q000002:abnormalities / Q000196:embryology* / Q000378:metabolism; D051157:Frizzled Receptors; D018507:Gene Expression Regulation, Developmental; D005822:Genetic Vectors; D017403:In Situ Hybridization; D010641:Phenotype; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology*; D012190:Retroviridae / Q000235:genetics; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014722:Vestibule, Labyrinth / Q000002:abnormalities / Q000196:embryology / Q000378:metabolism; D051153:Wnt Proteins; D060528:Wnt4 Protein; D029961:Zebrafish Proteins; D051176:beta Catenin
D003598:Cytoskeletal Proteins; D051157:Frizzled Receptors; D011506:Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D060528:Wnt4 Protein; D029961:Zebrafish Proteins; D051176:beta Catenin