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Development. 2019 Feb 15;146(4). pii: dev174748. doi: 10.1242/dev.174748.

Genetic interactions support an inhibitory relationship between bone morphogenetic protein 2 and netrin 1 during semicircular canal formation.

Author information

1
National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Porter Neuroscience Research Center, Bethesda, MD 20892, USA.
2
National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Porter Neuroscience Research Center, Bethesda, MD 20892, USA wud@nidcd.nih.gov.

Abstract

The semicircular canals of the mammalian inner ear are derived from epithelial pouches in which epithelial cells in the central region of each pouch undergo resorption, leaving behind the region at the rim to form a tube-shaped canal. Lack of proliferation at the rim and/or over-clearing of epithelial cells in the center of the pouch can obliterate canal formation. Otic-specific knockout of bone morphogenetic protein 2 (Bmp2) results in absence of all three semicircular canals; however, the common crus and ampullae housing the sensory tissue (crista) are intact. The lack of Bmp2 causes Ntn1 (which encodes netrin 1), which is required for canal resorption, to be ectopically expressed at the canal rim. Ectopic Ntn1 results in reduction of Dlx5 and Lmo4, which are required for rim formation. These phenotypes can be partially rescued by removing one allele of Ntn1 in the Bmp2 mutants, indicating that Bmp2 normally negatively regulates Ntn1 for canal formation. Additionally, non-resorption of the canal pouch in Ntn1-/- mutants is partially rescued by removing one allele of Bmp2 Thus, reciprocal inhibition between Bmp2 and netrin 1 is involved in canal formation of the vestibule.

KEYWORDS:

Inner ear; Morphogenesis; Mouse; Patterning

PMID:
30770380
DOI:
10.1242/dev.174748
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Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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