title: Proliferation-independent regulation of organ size by Fgf/Notch signaling.
abstract: Organ morphogenesis depends on the precise orchestration of cell migration, cell shape changes and cell adhesion. We demonstrate that Notch signaling is an integral part of the Wnt and Fgf signaling feedback loop coordinating cell migration and the self-organization of rosette-shaped sensory organs in the zebrafish lateral line system. We show that Notch signaling acts downstream of Fgf signaling to not only inhibit hair cell differentiation but also to induce and maintain stable epithelial rosettes. Ectopic Notch expression causes a significant increase in organ size independently of proliferation and the Hippo pathway. Transplantation and RNASeq analyses revealed that Notch signaling induces apical junctional complex genes that regulate cell adhesion and apical constriction. Our analysis also demonstrates that in the absence of patterning cues normally provided by a Wnt/Fgf signaling system, rosettes still self-organize in the presence of Notch signaling.
authors.affiliation: Stowers Institute for Medical Research, Kansas City, United States.
authors.forename: Agnė
authors.initials: A
authors.lastname: Kozlovskaja-Gumbrienė
authors.affiliation: Stowers Institute for Medical Research, Kansas City, United States.
authors.forename: Ren
authors.initials: R
authors.lastname: Yi
authors.affiliation: Stowers Institute for Medical Research, Kansas City, United States.
authors.forename: Richard
authors.initials: R
authors.lastname: Alexander
authors.affiliation: Stowers Institute for Medical Research, Kansas City, United States.
authors.forename: Andy
authors.initials: A
authors.lastname: Aman
authors.affiliation: Stowers Institute for Medical Research, Kansas City, United States.
authors.forename: Ryan
authors.initials: R
authors.lastname: Jiskra
authors.affiliation: Developmental Genetics Program and Kimmel Center for Stem Cell Biology, Skirball Institute of Biomolecular Medicine, New York University Langone Medical Center, New York, United States.
authors.forename: Danielle
authors.initials: D
authors.lastname: Nagelberg
authors.affiliation: Developmental Genetics Program and Kimmel Center for Stem Cell Biology, Skirball Institute of Biomolecular Medicine, New York University Langone Medical Center, New York, United States.
authors.forename: Holger
authors.initials: H
authors.lastname: Knaut
authors.affiliation: Stowers Institute for Medical Research, Kansas City, United States.
authors.forename: Melainia
authors.initials: M
authors.lastname: McClain
authors.affiliation: Stowers Institute for Medical Research, Kansas City, United States.
authors.forename: Tatjana
authors.identifier: 0000-0001-8098-2574
authors.initials: T
authors.lastname: Piotrowski
mesh_terms: D000818:Animals; D009024:Morphogenesis; D009929:Organ Size; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D015027:Zebrafish / Q000196:embryology*
chemical_list: D017468:Receptors, Fibroblast Growth Factor; D051880:Receptors, Notch
keywords: Hippo pathway; apical constriction; cell adhesion; cell biology; collective cell migration; developmental biology; lateral line system; rosettes; stem cells; zebrafish