ANTINEUROGENIC PHENOTYPES INDUCED BY TRUNCATED NOTCH PROTEINS INDICATE A ROLE IN SIGNAL-TRANSDUCTION AND MAY POINT TO A NOVEL FUNCTION FOR NOTCH IN NUCLEI
T. Lieber et al., ANTINEUROGENIC PHENOTYPES INDUCED BY TRUNCATED NOTCH PROTEINS INDICATE A ROLE IN SIGNAL-TRANSDUCTION AND MAY POINT TO A NOVEL FUNCTION FOR NOTCH IN NUCLEI, Genes & development, 7(10), 1993, pp. 1949-1965
Loss of any one of several neurogenic genes of Drosophila results in o
verproduction of embryonic neuroblasts at the expense of epidermoblast
s. In this paper a variety of altered Notch proteins are expressed in
transgenic flies. Dominant lethal, antineurogenic phenotypes were prod
uced by expression of three classes of mutant proteins: (1) a protein
comprised of the cytoplasmic domain of Notch and devoid of sequences p
ermitting membrane association; (2) a transmembrane protein lacking th
e extracellular, lin12/Notch repeats; and (3) transmembrane proteins c
arrying amino acid substitutions replacing one or both extracellular c
ysteines thought to be involved in Notch dimerization. These Notch pro
teins not only suppress the neural hypertrophy observed in Notch- embr
yos, but also generate a phenotype in which elements of the embryonic
nervous system are underproduced. Action of the intracellular cdc10 re
peats appears to be essential for wild-type Notch function or for the
antineurogenic activity of these proteins. The activities of the domin
ant, gain-of-function proteins indicate that Notch functions as a sign
al transducing receptor during ectoderm development. Production of ant
ineurogenic Notch proteins in embryos deficient for the other neurogen
ic genes allowed functional dependencies to be established. Delta, mas
termind, bigbrain, and neuralized appear to function in elaboration of
a signal upstream of Notch. Genes of the Enhancer of split complex ac
t after Notch. The cytoplasmic domain of Notch contains nuclear locali
zation sequences that function in cultured cells, and one of the Notch
antineurogenic proteins, the cytoplasmic domain, accumulates in nucle
i in vivo.