title: Kremen1 regulates mechanosensory hair cell development in the mammalian cochlea and the zebrafish lateral line.
abstract: Here we present spatio-temporal localization of Kremen1, a transmembrane receptor, in the mammalian cochlea, and investigate its role in the formation of sensory organs in mammal and fish model organisms. We show that Kremen1 is expressed in prosensory cells during cochlear development and in supporting cells of the adult mouse cochlea. Based on this expression pattern, we investigated whether Kremen1 functions to modulate cell fate decisions in the prosensory domain of the developing cochlea. We used gain and loss-of-function experiments to show that Kremen1 is sufficient to bias cells towards supporting cell fate, and is implicated in suppression of hair cell formation. In addition to our findings in the mouse cochlea, we examined the effects of over expression and loss of Kremen1 in the zebrafish lateral line. In agreement with our mouse data, we show that over expression of Kremen1 has a negative effect on the number of mechanosensory cells that form in the zebrafish neuromasts, and that fish lacking Kremen1 protein develop more hair cells per neuromast compared to wild type fish. Collectively, these data support an inhibitory role for Kremen1 in hair cell fate specification.
authors.affiliation: Biological Sciences, Sunnybrook Research Institute, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada.
authors.forename: Joanna F
authors.initials: JF
authors.lastname: Mulvaney
authors.affiliation: College of Arts and Sciences and Department of Integrative Physiology and Neuroscience, Washington State University, Vancouver, WA, USA.
authors.forename: Cathrine
authors.initials: C
authors.lastname: Thompkins
authors.affiliation: Biological Sciences, Sunnybrook Research Institute, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada.
authors.forename: Teppei
authors.initials: T
authors.lastname: Noda
authors.affiliation: Biological Sciences, Sunnybrook Research Institute, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada.
authors.forename: Koji
authors.initials: K
authors.lastname: Nishimura
authors.affiliation: Biological Sciences, Sunnybrook Research Institute, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada.
authors.forename: Willy W
authors.initials: WW
authors.lastname: Sun
authors.affiliation: Department of Surgery, School of Medicine, University of California San Diego, La Jolla, CA, USA.
authors.forename: Shuh-Yow
authors.initials: SY
authors.lastname: Lin
authors.affiliation: College of Arts and Sciences and Department of Integrative Physiology and Neuroscience, Washington State University, Vancouver, WA, USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Coffin
authors.affiliation: Biological Sciences, Sunnybrook Research Institute, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada.|Department of Otolaryngology - Head and Neck Surgery, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
authors.forename: Alain
authors.initials: A
authors.lastname: Dabdoub
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002454:Cell Differentiation / Q000235:genetics; D003051:Cochlea / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006198:Hair Cells, Auditory / Q000378:metabolism*; D053403:Lateral Line System / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D008465:Mechanoreceptors / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009154:Mutation; D055495:Neurogenesis / Q000235:genetics; D034622:RNA Interference; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D029961:Zebrafish Proteins; C486077:Kremen1 protein, mouse; C000592421:kremen1 protein, zebrafish