title: Regeneration of Sensory Hair Cells Requires Localized Interactions between the Notch and Wnt Pathways.
abstract: In vertebrates, mechano-electrical transduction of sound is accomplished by sensory hair cells. Whereas mammalian hair cells are not replaced when lost, in fish they constantly renew and regenerate after injury. In vivo tracking and cell fate analyses of all dividing cells during lateral line hair cell regeneration revealed that support and hair cell progenitors localize to distinct tissue compartments. Importantly, we find that the balance between self-renewal and differentiation in these compartments is controlled by spatially restricted Notch signaling and its inhibition of Wnt-induced proliferation. The ability to simultaneously study and manipulate individual cell behaviors and multiple pathways in vivo transforms the lateral line into a powerful paradigm to mechanistically dissect sensory organ regeneration. The striking similarities to other vertebrate stem cell compartments uniquely place zebrafish to help elucidate why mammals possess such low capacity to regenerate hair cells.
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA; Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT 84132, USA.
authors.forename: Andrés
authors.initials: A
authors.lastname: Romero-Carvajal
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Navajas Acedo
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Linjia
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Agnė
authors.initials: A
authors.lastname: Kozlovskaja-Gumbrienė
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Alexander
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA; Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT 84132, USA. Electronic address: pio@stowers.org.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Piotrowski
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D006198:Hair Cells, Auditory / Q000502:physiology*; D008465:Mechanoreceptors / Q000378:metabolism; D051880:Receptors, Notch / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000502:physiology; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: D051880:Receptors, Notch; D051153:Wnt Proteins; D029961:Zebrafish Proteins