title: Lef1 regulates Dusp6 to influence neuromast formation and spacing in the zebrafish posterior lateral line primordium.
abstract: The posterior lateral line primordium (PLLp) migrates caudally and periodically deposits neuromasts. Coupled, but mutually inhibitory, Wnt-FGF signaling systems regulate proto-neuromast formation in the PLLp: FGF ligands expressed in response to Wnt signaling activate FGF receptors and initiate proto-neuromast formation. FGF receptor signaling, in turn, inhibits Wnt signaling. However, mechanisms that determine periodic neuromast formation and deposition in the PLLp remain poorly understood. Previous studies showed that neuromasts are deposited closer together and the PLLp terminates prematurely in lef1-deficient zebrafish embryos. It was suggested that this results from reduced proliferation in the leading domain of the PLLp and/or premature incorporation of progenitors into proto-neuromasts. We found that rspo3 knockdown reduces proliferation in a manner similar to that seen in lef1 morphants. However, it does not cause closer neuromast deposition or premature termination of the PLLp, suggesting that such changes in lef1-deficient embryos are not linked to changes in proliferation. Instead, we suggest that they are related to the role of Lef1 in regulating the balance of Wnt and FGF functions in the PLLp. Lef1 determines expression of the FGF signaling inhibitor Dusp6 in leading cells and regulates incorporation of cells into neuromasts; reduction of Dusp6 in leading cells in lef1-deficient embryos allows new proto-neuromasts to form closer to the leading edge. This is associated with progressively slower PLLp migration, reduced spacing between deposited neuromasts and premature termination of the PLLp system.
authors: Program in Genomics of Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20852, USA.
authors: Miho
authors: M
authors: Matsuda
authors: Damian Dalle
authors: DD
authors: Nogare
authors: Katherine
authors: K
authors: Somers
authors: Kathleen
authors: K
authors: Martin
authors: Chongmin
authors: C
authors: Wang
authors: Ajay B
authors: AB
authors: Chitnis
mesh_terms: D000818:Animals; D019521:Body Patterning; D049109:Cell Proliferation; D054642:Dual Specificity Phosphatase 6 / Q000235:genetics / Q000378:metabolism*; D051526:Fibroblast Growth Factor 10 / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D053403:Lateral Line System / Q000196:embryology*; D008024:Ligands; D009154:Mutation; D019699:Thrombospondins; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D060449:Wnt Signaling Pathway; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D051526:Fibroblast Growth Factor 10; C507321:LEF1 protein, zebrafish; D008024:Ligands; C556668:RSPO1 protein, zebrafish; D019699:Thrombospondins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C520413:fgf10a protein, zebrafish; D049452:Green Fluorescent Proteins; D054642:Dual Specificity Phosphatase 6
keywords: Dusp6; FGF; Lateral line; Lef1; R-spondin; Wnt; Zebrafish
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