PubMed Health⌕ Search

Biomedical subjects

T N Scottgale

Publications and source records attributed to T N Scottgale.

3 recordsLinked to original sources

The gene Serrate encodes a putative EGF-like transmembrane protein essential for proper ectodermal development in Drosophila melanogaster.

Mutations in the third chromosome gene Serrate are shown to display genetic interactions with specific alleles of the neurogenic locus Notch, which encodes a transmembrane protein with epidermal growth factor (EGF) homology. Embryonic lethal Serrate mutations exhibit epidermal and neuronal defects, which are reminiscent of those produced by mutations in the Drosophila EGF receptor homolog gene. We present the molecular cloning of Serrate and show that it encodes two coordinately expressed transcripts from a genomic interval greater than 30 kb in length. The deduced protein product of 1404 amino acids contains a single transmembrane domain and 14 EGF-like repeats. Thus, Serrate represents another member of the group of EGF-containing loci in Drosophila. Whole-mount in situ hybridization analysis reveals complex temporal and spatial patterns of RNA expression consistent with the epidermal and neuronal defects observed in mutant embryos. Finally, we discuss the implications of Serrate function within the context of other cell-surface molecules known to be involved in the differentiation of ectodermally derived tissues.

Alleles↗

The Notch locus and the genetic circuitry involved in early Drosophila neurogenesis.

The genetic and molecular analysis of the Notch locus, which codes for a transmembrane protein sharing homology with the mammalian epidermal growth factor, suggests that the Notch protein is involved in a cell interaction mechanism essential for the differentiation of the embryonic nervous system of Drosophila. Taking advantage of the negative complementation between two Notch mutations that affect the extracellular domain of the protein, we have tried to dissect the genetic circuitry in which Notch is integrated by searching for genes whose products may interact with the Notch protein. This genetic screen has led to the identification of a surprisingly restricted set of interacting loci, including Delta and mastermind. Like Notch, both of these genes belong to a group of loci, the neurogenic loci, which have been previously identified by virtue of their similar mutant phenotype affecting early neurogenesis. We extend these studies by systematically exploring interactions between specific mutations in the Notch molecule and the other neurogenic genes. Furthermore, we show that the molecular lesions of two Notch alleles (nd and nd2), which interact dramatically with mastermind mutations, as well as with a mutation affecting the transducin homologous product of the neurogenic locus Enhancer of split, involve changes in the intracellular domain of the protein.

Alleles↗

Physical and functional definition of the Drosophila Notch locus by P element transformation.

Notch is a developmentally regulated locus which controls the differentiation of various Drosophila tissues, among them the embryonic nervous system. Molecular analysis has suggested that Notch is defined by an approximately 40-kb transcription unit which is spliced into a 10.2-kb mRNA composed of nine exonic regions and coding for a 2703-amino acid long transmembrane protein that shows homology to the mammalian epidermal growth factor. Here, we define the 5' end of the transcription unit and determine the sequences deleted in a Notch mutation involving the 5' nontranscribed region. Using a Notch cosmid vector we demonstrate by P element-mediated transformation that all sequences necessary for Notch function are confined in an approximately 40-kb long genomic region. cDNA sequences are used to construct a 15-kb "minigene" which lacks most, but not all, introns and its functionality is also tested by P element transformation. We show that, unlike the cosmid vector which is capable of rescuing completely all Notch mutations, only certain phenotypes can be rescued by the "minigene." The functional implications of our findings are discussed.

Animals↗