Suppression of neural fate and control of inner ear morphogenesis by Tbx1.
Inner ear sensory organs and VIIIth cranial ganglion neurons of the auditory/vestibular pathway derive from an ectodermal placode that invaginates to form an otocyst. We show that in the mouse otocyst epithelium, Tbx1 suppresses neurogenin 1-mediated neural fate determination and is required for induction or proper patterning of gene expression related to sensory organ morphogenesis (Otx1 and Bmp4, respectively). Tbx1 loss-of-function causes dysregulation of neural competence in otocyst regions linked to the formation of either mechanosensory or structural sensory organ epithelia. Subsequently, VIIIth ganglion rudiment form is duplicated posteriorly, while the inner ear is hypoplastic and shows neither a vestibular apparatus nor a coiled cochlear duct. We propose that Tbx1 acts in the manner of a selector gene to control neural and sensory organ fate specification in the otocyst.
Raft
Steven
S
Department of Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Nowotschin
Sonja
S
Liao
Jun
J
Morrow
Bernice E
BE
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D007758:Ear, Inner / Q000196:embryology* / Q000378:metabolism; D018257:Helix-Loop-Helix Motifs / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*
D019485:Bone Morphogenetic Proteins; D020825:T-Box Domain Proteins; C491573:Tbx1 protein, mouse