Nucleotide sequence from the neurogenic locus Notch implies a gene product that shares homology with proteins containing EGF-like repeats

doi:10.1016/0092-8674(85)90229-6

Cell

Volume 43, Issue 3, Part 2, December 1985, Pages 567-581

https://doi.org/10.1016/0092-8674(85)90229-6 Get rights and content

Abstract

The primary structure of the major embryonic Notch transcript is presented, as determined by sequence analysis of overlapping cDNA clones. The 10,148 bp sequence corresponding to this transcript possesses an 8109 bp open reading frame that potentially codes for a 2703 amino acid protein. We show that this polypeptide contains a repeated structure composed of 36 tandemly arranged 40 amino acid long repeats, which show homology to the epidermal growth factor and other proteins containing EGF-like repeats. Hydropathy plots suggest that the putative Notch protein may span the membrane. We relate these findings to the developmental action of Notch and speculate that the locus may be involved in a cell-cell interaction mechanism that is essential for the differentiation of the ectoderm into neural and epidermal precursors.

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The Notch signaling pathway, an evolutionarily highly conserved pathway, participates in various essential physiological processes in organisms. Activation of Notch signaling in the canonical manner requires the combination of ligand and receptor. There are two ligands of Notch in Drosophila: Delta (Dl) and Serrate (Ser). A mutation mf157 is identified for causing nicks of fly wings in genetic analysis from a mutant library (unpublished) that was established previously. Immunofluorescent staining illustrates that mf157 represses the expression of Cut and Wingless (Wg), the targets of Notch signaling. MARCM cloning analysis reveals that mf157 functions at the same level or the upstream of ligands of Notch in signaling sending cells. Sequencing demonstrates that mf157 is a novel allele of the Ser gene. Subsequently, mf553 and mf167 are also identified as new alleles of Ser from our library. Furthermore, the complementary assays and the examination of transcripts confirm the sequencing results. Besides, the repressed phenotypes of Notch signaling were reverted by transposon excision experiments of mf157. In conclusion, we identify three fresh alleles of Ser. Our works supply additional genetic resources for further study of functions of Ser and Notch signaling regulation.
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Citation Excerpt :
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Cell

ArticleNucleotide sequence from the neurogenic locus Notch implies a gene product that shares homology with proteins containing EGF-like repeats

Abstract

TINS

Cell

Dev. Biol.

Dev. Biol.

Trends Biochem. Sci.

Dev. Biol.

Cell

J. Mol. Biol.

Gene

J. Mol. Biol.

Cell

J. Mol. Biol.

Cell

Science

Cell

Science

Roux's Arch. Dev. Biol.

Molecular cloning of Notch, a locus affecting neurogenesis in Drosophila melanogaster

Segmental distribution of bithorax complex proteins during Drosophila development

Nature

Buffer gradient gels and 35S label as an aid to rapid DNA sequence determination

Vaccinia virus 19-kilodalton protein: relationship to several mammalian proteins, including two growth factors

Vaccinia virus encodes a peptide homologous to epidermal growth factor and transforming growth factor

Nature

A genetic analysis of early neurogenesis in Drosophila

Epidermal growth factor

Ann. Rev. Biochem.

Empirical predictions of protein conformation

Ann. Rev. Biochem.

pEMBL: a new family of single stranded plasmids

Nucl. Acids Res.

A comprehensive set of sequence programs for the VAX

Nucl. Acids Res.

Computer-based characterization of epidermal growth factor precursor

Nature

Recognition of protein coding regions in DNA sequences

Nucl. Acids Res.

Characterization of a cDNA coding for human protein C

The nucleotide sequence of the gene for human protein C

Negative complementation at the Notch locus of Drosophila melanogaster

Genetics

A subcloning strategy for DNA sequence analysis

Nucl. Acids Res.

Protein sequence plotting program: PRPLOT

Article
Nucleotide sequence from the neurogenic locus Notch implies a gene product that shares homology with proteins containing EGF-like repeats

Buffer gradient gels and ³⁵S label as an aid to rapid DNA sequence determination