Sox9 is required for invagination of the otic placode in mice.
The HMG-domain-containing transcription factor Sox9 is an important regulator of chondrogenesis, testis formation and development of several other organs. Sox9 is expressed in the otic placodes, the primordia of the inner ear, and studies in Xenopus have provided evidence that Sox9 is required for otic specification. Here we report novel and different functions of Sox9 during mouse inner ear development. We show that in mice with a Foxg1(Cre)-mediated conditional inactivation of Sox9 in the otic ectoderm, otic placodes form and express markers of otic specification. However, mutant placodes do not attach to the neural tube, fail to invaginate, and subsequently degenerate by apoptosis, resulting in a complete loss of otic structures. Transmission-electron microscopic analysis suggests that cell-cell contacts in the Sox9 mutant placodes are abnormal, although E-cadherin, N-cadherin, and beta-catenin protein expression are unchanged. In contrast, expression of Epha4 was downregulated in mutant placodes. In embryos with a Keratin-19(Cre)-mediated mosaic inactivation of Sox9, Sox9-negative and Sox9-positive cells in the otic ectoderm sort out from one another. In these embryos only Sox9-positive cells invaginate and form one or several micro-vesicles, whereas Sox9-negative cells stay behind and die. Our findings demonstrate that, in contrast to Xenopus, Sox9 is not required for the initial specification of the otic placode in the mouse, but instead controls adhesive properties and invagination of placodal cells in a cell-autonomous manner.
Barrionuevo
Francisco
F
Institute of Human Genetics and Anthropology, University of Freiburg, Breisacherstr. 33, D-79106 Freiburg, Germany. francisco.barrionuevo@uniklinik-freiburg.de
Naumann
Angela
A
Bagheri-Fam
Stefan
S
Speth
Volker
V
Taketo
Makoto M
MM
Scherer
Gerd
G
Neubüser
Annette
A
D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D007758:Ear, Inner / Q000166:cytology / Q000196:embryology*; D004475:Ectoderm / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D036122:Receptor, EphA4 / Q000378:metabolism; D055758:SOX9 Transcription Factor; D055757:SOXE Transcription Factors; D013136:Spiral Ganglion / Q000166:cytology / Q000196:embryology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D055758:SOX9 Transcription Factor; D055757:SOXE Transcription Factors; C527924:Sox10 protein, mouse; C527933:Sox9 protein, mouse; D014157:Transcription Factors; D036122:Receptor, EphA4