During development, morphogenetic processes require a precise coordination of cell differentiation, cell shape changes and, often, cell migration. Yet, how pattern information is used to orchestrate these different processes is still unclear. During lateral line (LL) morphogenesis, a group of cells simultaneously migrate and assemble radially organized cell clusters, termed rosettes, that prefigure LL sensory organs. This process is controlled by Fibroblast growth factor (FGF) signalling, which induces cell fate changes, cell migration and cell shape changes. However, the exact molecular mechanisms induced by FGF activation that mediate these changes on a cellular level are not known. Here, we focus on the mechanisms by which FGFs control apical constriction and rosette assembly. We show that apical constriction in the LL primordium requires the activity of non-muscle myosin. We demonstrate further that shroom3, a well-known regulator of non-muscle myosin activity, is expressed in the LL primordium and that its expression requires FGF signalling. Using gain- and loss-of-function experiments, we demonstrate that Shroom3 is the main organizer of cell shape changes during rosette assembly, probably by coordinating Rho kinase recruitment and non-muscle myosin activation. In order to quantify morphogenesis in the LL primordium in an unbiased manner, we developed a unique trainable 'rosette detector'. We thus propose a model in which Shroom3 drives rosette assembly in the LL downstream of FGF in a Rho kinase- and non-muscle myosin-dependent manner. In conclusion, we uncovered the first mechanistic link between patterning and morphogenesis during LL sensory organ formation.
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http://dx.doi.org/10.1242/dev.083253 | DOI Listing |
Biochemistry
January 2025
Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, Maryland 20742, United States.
Sci Rep
January 2025
Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA.
α-Klotho (KLA) is a type-1 membranous protein that can associate with fibroblast growth factor receptor (FGFR) to form co-receptor for FGF23. The ectodomain of unassociated KLA is shed as soluble KLA (sKLA) to exert FGFR/FGF23-independent pleiotropic functions. The previously determined X-ray crystal structure of the extracellular region of sKLA in complex with FGF23 and FGFR1c suggests that sKLA functions solely as an on-demand coreceptor for FGF23.
View Article and Find Full Text PDFAdv Sci (Weinh)
December 2024
School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Isoniazid and rifampicin co-therapy are the main causes of anti-tuberculosis drug-induced liver injury (ATB-DILI) and acute liver failure, seriously threatening human health. However, its pathophysiology is not fully elucidated. Growing evidences have shown that fibroblast growth factors (FGFs) play a critical role in diverse aspects of liver pathophysiology.
View Article and Find Full Text PDFbioRxiv
December 2024
Department of Orthopaedic Surgery, University of California - San Francisco, San Francisco, California, USA.
Background –: Previously we found that increasing fibroblast growth factor (FGF) signaling in the neural crest cells within the frontonasal process (FNP) of the chicken embryo caused dysmorphology that was correlated with reduced proliferation, disrupted cellular orientation, and lower MAPK activation but no change in PLCy and PI3K activation. This suggests RTK signaling may drive craniofacial morphogenesis through specific downstream effectors that affect cellular activities. In this study we inhibited three downstream branches of RTK signaling to determine their role in regulating cellular activities and how these changes affect morphogenesis of the FNP.
View Article and Find Full Text PDFJ Cell Mol Med
December 2024
Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy.
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