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Mechanosensory hair cells are essential for the perception of sound, motion and balance. The genetic pathways that regulate their differentiation from inner ear progenitors remain largely unknown. The hair cell-based lateral line system, found in fish and amphibians, aids in this endeavor as a valuable model to identify the genetic networks through which unspecialized cells acquire a hair cell specific fate. Here we present evidence that loss-of-function of orthodenticle homeobox proteins (Otx) introduces developmental changes that diminish hair cell differentiation capacity in posterior lateral line neuromasts of the zebrafish (Danio rerio). Gene knockdown experiments demonstrate that loss of otx1 or a combinatory double knockdown of any of the otx1, otx1-like or otx2 genes leads to a marked decrease in hair cells. Unlike the mammalian cochlea, which only generates hair cells during embryonic development, the zebrafish lateral line replaces lost hair cells throughout the animal’s life. Following hair cell ablation with copper sulfate, the regenerative hair cell differentiation program is impaired with fewer hair cells developing in either otx1 or otx2 single knockdown morphants or any otx1, otx1-like or otx2 double knockdown morphants. In sum, otx genes are required for normal hair cell differentiation in the zebrafish lateral line.
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Hannigan, Erin, "THE ROLE OF ORTHODENTICLE HOMEOBOX TRANSCRIPTION FACTORS IN THE DEVELOPMENT OF HAIR CELL SENSORY EPITHELIA" (2012). Senior Projects Spring 2012. 375.