Pax2 and Pax8 cooperate in mouse inner ear morphogenesis and innervation

BMC Developmental Biology - Tập 10 Số 1 - 2010
Maxime Bouchard1, Dominique de Caprona2, Meinrad Busslinger3, Pin-Xian Xu4, Bernd Fritzsch2
1Biochemistry Department, Goodman Cancer Centre, McGill University, Quebec, Canada
2Department of Biology, College of Liberal Arts and Sciences, 143 Biology Building, Iowa City, IA, 52242-1324, USA
3Research Institute of Molecular Pathology, Vienna BioCenter, Vienna, Austria
4Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine of New York University, New York, NY, 10029, USA

Tóm tắt

AbstractBackgroundPax2;5;8transcription factors play diverse roles in vertebrate and invertebrate organogenesis, including the development of the inner ear. Past research has suggested various cochlear defects and some vestibular defects inPax2null mice but the details of the cochlear defects and the interaction with otherPaxfamily members in ear development remain unclear.ResultsWe show thatPax2;8double null mice do not develop an ear past the otocyst stage and show little to no sensory as well as limited and transient neuronal development, thus indicating that these two family members are essential for overall ear morphogenesis and sustained neurosensory development. In support of functional redundancy between Pax proteins,Pax2can be substituted by aPax5minigene, a gene normally not expressed in the embryonic mouse ear. There is no detectable morphological defect inPax8null mice suggesting thatPax2expression can compensate forPax8. Conversely,Pax8cannot compensate forPax2leading to a cochlear phenotype not fully appreciated previously: Cochlear development is delayed until E15.5 when the cochlea extrudes as a large sack into the brain case. Immunocytochemistry and tracing from the brain show that a cochlear spiral ganglia form as a small addition to the inferior vestibular ganglion. However, the empty cochlear sack, devoid of any sensory epithelium development as indicated by the absence of Sox2 or MyoVII expression, nevertheless develop a dense innervation network of small neurons situated in the wall of the cochlear sack.ConclusionsCombined these data suggest thatPax2is needed for organ of Corti formation and is directly or indirectly involved in the coordination of spiral ganglion formation which is partially disrupted in thePax2null ears. All threePaxgenes can signal redundantly in the ear with their function being determined primarily by the spatio-temporal expression driven by the three distinct promoters of these genes.

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BMC Developmental Biology

Tập 10 Số 1

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