A MUTATION IN ZEBRAFISH AFFECTING A LOCALIZED CELLULAR FUNCTION REQUIRED FOR NORMAL EAR DEVELOPMENT

Zebrafish holds great potential as a model system for studying inner e ar development because genetic techniques are highly efficient and inn er ear development is a conspicuous and manipulable feature of zebrafi sh embryogenesis. Here we describe analysis of a semilethal dominant m utation, termed monolith (mn1), that specifically perturbs formation o f the anterior (utricular) otolith in the developing ear. Other than t he utricular otolith deficiency, all structures in the ear appear morp hologically normal in mutant embryos, including posterior otoliths and all sensory epithelia. Expression patterns of several ear marker gene s (msxC, msxD, and d1x3) also appear normal in the mutant. To identify the cell type(s) affected by the mn1 mutation, chimeras were generate d by transplanting dye-labeled +/+ cells into unlabeled mn1/mn1 host e mbryos. Roughly half of such chimeras formed utricular otoliths normal ly, indicating that the transplanted wild-type cells rescued their mut ant hosts. Detailed analysis of +/+ cell fates revealed that virtually all chimeras in which +/+ cells formed support cells in the utricular sensory epithelium were rescued. In contrast, wild-type cells forming other cell types (such as hair cells) or colonizing other regions of the host were not sufficient to facilitate rescue. These data indicate that support cells are required for normal otolith formation, providi ng the first experimentally established role for support cells in vert ebrate sensory epithelia. The data also provide tile first clear indic ation that otolith formation is controlled independently in different regions of the ear by localized cellular functions. (C) 1996 Academic Press, Inc.