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Apical membrane maturation and cellular rosette formation during morphogenesis of the zebrafish lateral line.

ABSTRACT: Tissue morphogenesis and cell sorting are major forces during organ development. Here, we characterize the process of tissue morphogenesis within the zebrafish lateral line primordium, a migratory sheet of cells that gives rise to the neuromasts of the posterior lateral line organ. We find that cells within this epithelial tissue constrict actin-rich membranes and enrich apical junction proteins at apical focal points. The coordinated apical membrane constriction in single Delta D-positive hair cell progenitors and in their neighbouring prospective support cells generates cellular rosettes. Live imaging reveals that cellular rosettes subsequently separate from each other and give rise to individual neuromasts. Genetic analysis uncovers an involvement of Lethal giant larvae proteins in the maturation of apical junction belts during cellular rosette formation. Our findings suggest that apical constriction of cell membranes spatially confines regions of strong cell-cell adhesion and restricts the number of tightly interconnected cells into cellular rosettes, which ensures the correct deposition of neuromasts during morphogenesis of the posterior lateral line organ.

SUBMITTER: Hava D

PROVIDER: S-EPMC3188803 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Apical membrane maturation and cellular rosette formation during morphogenesis of the zebrafish lateral line.

Hava David D Forster Ulrike U Matsuda Miho M Cui Shuang S Link Brian A BA Eichhorst Jenny J Wiesner Burkhard B Chitnis Ajay A Abdelilah-Seyfried Salim S

Journal of cell science 20090210 Pt 5

Tissue morphogenesis and cell sorting are major forces during organ development. Here, we characterize the process of tissue morphogenesis within the zebrafish lateral line primordium, a migratory sheet of cells that gives rise to the neuromasts of the posterior lateral line organ. We find that cells within this epithelial tissue constrict actin-rich membranes and enrich apical junction proteins at apical focal points. The coordinated apical membrane constriction in single Delta D-positive hair ...[more]

PMID: 19208766

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Project description:The zebrafish is a valuable model for studying hair cell development, structure, genetics, and behavior. Zebrafish and other aquatic vertebrates have hair cells on their body surface organized into a sensory system called the lateral line. These hair cells are highly accessible and easily visualized using fluorescent dyes. Morphological and functional similarities to mammalian hair cells of the inner ear make the zebrafish a powerful preparation for studying hair cell toxicity. The ototoxic potential of drugs has historically been uncovered by anecdotal reports that have led to more formal investigation. Currently, no standard screen for ototoxicity exists in drug development. Thus, for the vast majority of Food and Drug Association (FDA)-approved drugs, the ototoxic potential remains unknown. In this study, we used 5-day-old zebrafish larvae to screen a library of 1,040 FDA-approved drugs and bioactives (NINDS Custom Collection II) for ototoxic effects in hair cells of the lateral line. Hair cell nuclei were selectively labeled using a fluorescent vital dye. For the initial screen, fish were exposed to drugs from the library at a 100-muM concentration for 1 h in 96-well tissue culture plates. Hair cell viability was assessed in vivo using fluorescence microscopy. One thousand forty drugs were rapidly screened for ototoxic effects. Seven known ototoxic drugs included in the library, including neomycin and cisplatin, were positively identified using these methods, as proof of concept. Fourteen compounds without previously known ototoxicity were discovered to be selectively toxic to hair cells. Dose-response curves for all 21 ototoxic compounds were determined by quantifying hair cell survival as a function of drug concentration. Dose-response relationships in the mammalian inner ear for two of the compounds without known ototoxicity, pentamidine isethionate and propantheline bromide, were then examined using in vitro preparations of the adult mouse utricle. Significant dose-dependent hair cell loss in the mouse utricle was demonstrated for both compounds. This study represents an important step in validating the use of the zebrafish lateral line as a screening tool for the identification of potentially ototoxic drugs.

Dataset Information

Apical membrane maturation and cellular rosette formation during morphogenesis of the zebrafish lateral line.

Publications

Apical membrane maturation and cellular rosette formation during morphogenesis of the zebrafish lateral line.

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