title: Defects in sensory organ morphogenesis and generation of cochlear hair cells in Gata3-deficient mouse embryos.
abstract: The development of the inner ear sensory epithelia involves a complex network of transcription factors and signaling pathways and the whole process is not yet entirely understood. GATA3 is a DNA-binding factor that is necessary for otic morphogenesis and without GATA3 variable defects have been observed already at early stages in mouse embryos. In the less severe phenotypes, one small oval shaped vesicle is formed whereas in the more severe cases, the otic epithelium becomes disrupted and the endolymphatic domain becomes separated from the rest of the otic epithelium. Despite these defects, the early sensory fate specification occurs in Gata3-/- otic epithelium. However, due to the early lethality of Gata3-deficient embryos, the later morphogenesis and sensory development have remained unclear. To gain information of these later processes we produced drug-rescued Gata3-/- embryos that survived up to late gestation. In these older Gata3-/- embryos, a similar variability was observed as earlier. In the more severely affected ears, the development of the separate endolymphatic domain arrested completely whereas the remaining vesicle formed an empty cavity with variable forms, but without any distinguishable otic compartments or morphologically distinct sensory organs. However, the dorsal part of this vesicle was able to adopt a sensory fate and to produce some hair cells. In the less severe cases of Gata3-/- ears, distinct utricular, saccular and cochlear compartments were present and hair cells could be detected in the vestibular sensory epithelia. Although clear cristae and maculae formed, the morphology and size of these sensory areas were abnormal and they remained often un-separated. In contrast to the vestibule, the cochlear sensory compartment remained more immature and no hair or supporting cells could be detected. Our results suggest that GATA3 is critical for normal vestibular and cochlear morphogenesis and that it is especially important for cochlear sensory differentiation.
authors.affiliation: Department of Veterinary Biosciences, University of Helsinki, Agnes Sjobergin katu 2, 00790 Helsinki, Finland. maarja.haugas@helsinki.fi
authors.forename: Maarja
authors.initials: M
authors.lastname: Haugas
authors.forename: Kersti
authors.initials: K
authors.lastname: Lilleväli
authors.forename: Marjo
authors.initials: M
authors.lastname: Salminen
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000235:genetics; D002454:Cell Differentiation; D003051:Cochlea / Q000002:abnormalities / Q000196:embryology / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D050990:GATA3 Transcription Factor / Q000172:deficiency* / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D005865:Gestational Age; D006198:Hair Cells, Auditory / Q000378:metabolism* / Q000473:pathology; D018398:Homeodomain Proteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009024:Morphogenesis; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D050821:Transcription Factor Brn-3C / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D050990:GATA3 Transcription Factor; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D055748:SOXB1 Transcription Factors; D000072099:Serrate-Jagged Proteins; D050821:Transcription Factor Brn-3C; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein; C500943:Atoh1 protein, mouse; C494748:Gata3 protein, mouse; C121290:Pou4f3 protein, mouse; C527783:Sox2 protein, mouse