RESUMEN
Morphogenesis is a fascinating but complex and incompletely understood developmental process. The sensory lateral line system consists of only a few hundred cells and is experimentally accessible making it an excellent model system to interrogate the cellular and molecular mechanisms underlying segmental morphogenesis. The posterior lateral line primordium periodically deposits prosensory organs as it migrates to the tail tip. We demonstrate that periodic proneuromast deposition is governed by a fundamentally different developmental mechanism than the classical models of developmental periodicity represented by vertebrate somitogenesis and early Drosophila development. Our analysis demonstrates that proneuromast deposition is driven by periodic lengthening of the primordium and a stable Wnt/ß-catenin activation domain in the leading region of the primordium. The periodic lengthening of the primordium is controlled by Wnt/ß-catenin/Fgf-dependent proliferation. Once proneuromasts are displaced into the trailing Wnt/ß-catenin-free zone they are deposited. We have previously shown that Wnt/ß-catenin signaling induces Fgf signaling and that interactions between these two pathways regulate primordium migration and prosensory organ formation. Therefore, by coordinating migration, prosensory organ formation and proliferation, localized activation of Wnt/ß-catenin signaling in the leading zone of the primordium plays a crucial role in orchestrating lateral line morphogenesis.
Asunto(s)
Proliferación Celular , Sistema de la Línea Lateral/embriología , Morfogénesis/fisiología , Transducción de Señal/fisiología , Proteínas Wnt/metabolismo , Pez Cebra/embriología , beta Catenina/metabolismo , Animales , Afidicolina , Bromodesoxiuridina , Proliferación Celular/efectos de los fármacos , Cartilla de ADN/genética , Embrión no Mamífero/embriología , Factores de Crecimiento de Fibroblastos/metabolismo , Técnicas de Inactivación de Genes , Hidroxiurea , Hibridación in Situ , Etiquetado Corte-Fin in Situ , Pirroles/farmacología , Transducción de Señal/efectos de los fármacos , Imagen de Lapso de Tiempo , Factores de Transcripción/metabolismoRESUMEN
The distal region of neural retina (ciliary marginal zone [CMZ]) contains stem cells that produce non-neural and neuronal progenitors. We provide a detailed gene expression analysis of the eyes of apc mutant zebrafish where the Wnt/beta-catenin pathway is constitutively active. Wnt/beta-catenin signaling leads to an expansion of the CMZ accompanied by a central shift of the retinal identity gene sox2 and the proneural gene atoh7. This suggests an important role for peripheral Wnt/beta-catenin signaling in regulating the expression and localization of neurogenic genes in the central retina. Retinal identity genes rx1 and vsx2, as well as meis1 and pax6a act upstream of Wnt/beta-catenin pathway activation. Peripheral cells that likely contain stem cells can be identified by the expression of follistatin, otx1, and axin2 and the lack of expression of myca and cyclinD1. Our results introduce the zebrafish apc mutation as a new model to study signaling pathways regulating the CMZ.