THE NOVEL NOTCH HOMOLOG MOUSE NOTCH-3 LACKS SPECIFIC EPIDERMAL GROWTH FACTOR-REPEATS AND IS EXPRESSED IN PROLIFERATING NEUROEPITHELIUM

In Drosophila, the Notch gene is pivotal for cell fate decisions at many stages of development and, in particular, during the formation of the nervous system. Absence of Notch results in the generation of excessive numbers of neural cells at the expense of epidermal cells. Two previously identified mammalian Notch homologues encode all the principal features of the Drosophila gene, e.g. 36 EGF-repeats and 3 Notch/lin-12 repeats extracellularly and 6 intracellular cdc10/SW16 repeats. We report here the characterisation of a third,mammalian homologue, mouse Notch 3, which shares the same remarkable conservation relative to the Drosophila gene as the two previously identified homologues, but with three important distinctions. First, Notch 3 specifically lacks the equivalent of EGF-repeat 21; second, it lacks an EGF-repeat-sized region comprising parts of EGF-repeats 2 and 3; and third, it encodes a considerably shorter intracellular domain. The Notch 3 gene is expressed at high levels in proliferating neuroepithelium and expression is downregulated at later stages. The expression patterns of the Notch 1, 2 and 3 genes are quite distinct during central nervous system (CNS) development, and all possible combinations of expression, i.e. none, one, two, or all three genes, are seen, suggesting a combinatorial code of Notch function in mammals. Considering the predominantly early expression in CNS and its distinct structural features, the Notch 3 gene is likely to contribute significantly to vertebrate Notch function during CNS development.