title: Fgfr-Ras-MAPK signaling is required for apical constriction via apical positioning of Rho-associated kinase during mechanosensory organ formation.
abstract: Many morphogenetic movements during development require the formation of transient intermediates called rosettes. Within rosettes, cells are polarized with apical ends constricted towards the rosette center and nuclei basally displaced. Whereas the polarity and cytoskeletal machinery establishing these structures has been extensively studied, the extracellular cues and intracellular signaling cascades that promote their formation are not well understood. We examined how extracellular Fibroblast growth factor (Fgf) signals regulate rosette formation in the zebrafish posterior lateral line primordium (pLLp), a group of ∼100 cells that migrates along the trunk during embryonic development to form the lateral line mechanosensory system. During migration, the pLLp deposits rosettes from the trailing edge, while cells are polarized and incorporated into nascent rosettes in the leading region. Fgf signaling was previously shown to be crucial for rosette formation in the pLLp. We demonstrate that activation of Fgf receptor (Fgfr) induces intracellular Ras-MAPK, which is required for apical constriction and rosette formation in the pLLp. Inhibiting Fgfr-Ras-MAPK leads to loss of apically localized Rho-associated kinase (Rock) 2a, which results in failed actomyosin cytoskeleton activation. Using mosaic analyses, we show that a cell-autonomous Ras-MAPK signal is required for apical constriction and Rock2a localization. We propose a model whereby activated Fgfr signals through Ras-MAPK to induce apical localization of Rock2a in a cell-autonomous manner, activating the actomyosin network to promote apical constriction and rosette formation in the pLLp. This mechanism presents a novel cellular strategy for driving cell shape changes.
authors: Department of Cell and Developmental Biology, Oregon Health & Science University, Portland, OR 97239, USA.
authors: Molly J
authors: MJ
authors: Harding
authors: Alex V
authors: AV
authors: Nechiporuk
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002465:Cell Movement / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology*; D048430:Cell Shape / Q000502:physiology*; D005346:Fibroblast Growth Factors / Q000378:metabolism; D017403:In Situ Hybridization; D053403:Lateral Line System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D009024:Morphogenesis / Q000502:physiology*; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology*; D018631:ras Proteins / Q000378:metabolism
chemical_list: D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins