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Unformatted text preview: INTRODUCTION Neural development in vertebrates starts during gastrulation with the induction and patterning of the neural plate. The mor- phogenic transformation of the neural plate into the neural tube and the differentiation of neuronal cell types in different waves of neurogenesis follow. Finally, precise connection between neurons in the various brain regions are established. The com- plexity of this process is overwhelming, suggesting interactive mechanisms between cells and their neighbors or cells and their environment. The genetic control of many of these processes is not well understood in vertebrate organisms. In Drosophila , local cell-cell interactions play an important role in coordinating developmental decisions required for the gen- eration of different cell types (for reviews, Campos-Ortega, 1993; Ghysen et al., 1993). Neurogenic genes, such as Notch , Delta and others are involved in this process in many different tissues (Hartenstein et al., 1992). The products of these genes interact through lateral inhibition, committing a cell to a neural fate, and neighboring cells become epidermis (Seydoux and Greenwald, 1989; Heitzler and Simpson, 1991). Loss-of- function mutations cause overproduction of neurons – the neu- rogenic phenotype (Lehmann et al., 1983) – due to the mis- specification between the neural and epidermal pathways (Heitzler and Simpson, 1991). Gain-of-function mutations lead to overproduction of epidermis at the expense of neural struc- tures (Palka et al., 1990) and can be mimicked by extracellu- lar truncations of Notch (Struhl et al., 1993). Homologs of these genes have been cloned in vertebrates, such as Notch (Coffman et al., 1990; Weinmaster et al., 1991; Ellisen et al., 1991; Reaume et al., 1992 del Amo et al., 1992; Bierkamp and Campos-Ortega, 1993; Lardelli and Lendahl, 1993) Delta (Chitnis et al., 1995; Henrique et al., 1995; Bet- tenhausen et al., 1995) and a rat ligand for Notch (Lindsell et al., 1995). Misexpression of constitutively active forms of Notch in cultured mammalian cells suggests that it is involved 205 Development 123, 205-216 Printed in Great Britain © The Company of Biologists Limited 1996 DEV3374 In a screen for embryonic mutants in the zebrafish a large number of mutants were isolated with abnormal brain mor- phology. We describe here 26 mutants in 13 complementa- tion groups that show abnormal development of large regions of the brain. Early neurogenesis is affected in white tail (wit) . During segmentation stages, homozygous wit embryos display an irregularly formed neural keel, partic- ularly in the hindbrain. Using a variety of molecular markers, a severe increase in the number of various early differentiating neurons can be demonstrated. In contrast, late differentiating neurons, radial glial cells and some non- neural cell types, such as the neural crest-derived melanoblasts, are much reduced. Somitogenesis appears delayed. In addition, very reduced numbers of melanophores are present posterior to the mid-trunk. Themelanophores are present posterior to the mid-trunk....
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