Netrin 1 is required for semicircular canal formation in the mouse inner ear.
The morphogenetic development of the mammalian inner ear is a complex multistep process, the molecular and cellular details of which are only beginning to be unraveled. We show here that mouse netrin 1, known to be involved in axon guidance and cell migration in the central nervous system, also plays a critical morphogenetic role during semicircular canal formation. netrin 1 is expressed at high levels in the otic epithelium, in cells that will come together to form a fusion plate, a prerequisite for the formation of semicircular canals. In netrin 1 mutant mice, fusion plate formation is severely affected resulting in a reduced anterior semicircular canal and the complete lack of the posterior and lateral canals. Our results suggest that netrin 1 facilitates semicircular canal formation through two different mechanisms: (1) it participates in the detachment of the fusion plate epithelia from the basement membrane, and (2) it stimulates proliferation of the periotic mesenchymal cells which then push the epithelial cell walls together to form the fusion plate.
Salminen
M
M
Department of Molecular Cell Biology, Max Planck Institute of Biophysical Chemistry, Göttingen, Germany.
Meyer
B I
BI
Bober
E
E
Gruss
P
P
D000483:Alleles; D000818:Animals; D002455:Cell Division; D004423:Ear / Q000196:embryology; D004848:Epithelium / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D008297:Male; D008648:Mesoderm; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009414:Nerve Growth Factors / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D000075388:Netrin-1; D012665:Semicircular Canals / Q000196:embryology*; D025521:Tumor Suppressor Proteins
C086187:Hmx3 protein, mouse; D018398:Homeodomain Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C000617353:Ntn1 protein, mouse; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1