Murine homologs of deltex define a novel gene family involved in vertebrate Notch signaling and neurogenesis

Int J Dev Neurosci. 2001 Feb;19(1):21-35. doi: 10.1016/s0736-5748(00)00071-x.

Abstract

Notch signaling plays an important role in cell-fate specification in multicellular organisms by regulating cell-cell communication. The Drosophila deltex gene encodes a modulator of the Notch pathway that has been shown to interact physically with the Ankyrin repeats of Notch. We isolated four distinct cDNAs corresponding to mouse homologs of deltex - mouse Deltex1 (MDTX1), mouse Deltex2 (MDTX2), mouse Deltex2DeltaE (MDTX2DeltaE), and mouse Deltex3 (MDTX3). Deduced amino acid sequences of these four cDNAs showed a high degree of similarity to Drosophila Deltex and its human homolog, DTX1 throughout their lengths, even though they possess distinct structural features. MDTX proteins formed homotypic and heterotypic multimers. We found that these genes were expressed in the central, peripheral nervous system and in the thymus, overlapping with those of mouse Notch1. In mammalian tissue culture cells, overexpression of any of the four mouse deltex homologs suppressed the transcriptional activity of E47, a basic helix-loop-helix (bHLH) protein, in a manner similar to suppression by an activated form of human Notch1 or human DTX1. In addition, overexpression of MDTX2 and MDTX2DeltaE in C2C12 cells under differentiation-inducing conditions suppressed the expression of myogenin, one of the myogenic transcriptional factors; this was also similar to a previously reported activity of constitutively activated Notch. Furthermore, misexpression of any of the MDTX genes in Xenopus embryos resulted in an expansion of the region expressing the neural cell adhesion molecule (N-CAM) gene, a marker for the neuroepithelium. Collectively, our results suggest that these mouse deltex homologs are involved in vertebrate Notch signaling and regulation of neurogenesis.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Carrier Proteins*
  • Cell Differentiation / genetics*
  • Cell Lineage / genetics*
  • Cells, Cultured / cytology
  • Cells, Cultured / metabolism
  • DNA, Complementary / chemistry
  • DNA, Complementary / isolation & purification
  • DNA, Complementary / metabolism
  • Drosophila Proteins*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / embryology
  • Embryo, Mammalian / metabolism
  • Embryo, Nonmammalian
  • Female
  • Gene Expression Regulation, Developmental / genetics
  • Insect Proteins / genetics*
  • Insect Proteins / metabolism
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Mice
  • Molecular Sequence Data
  • Nervous System / cytology
  • Nervous System / embryology*
  • Nervous System / metabolism
  • Neural Cell Adhesion Molecules / metabolism
  • Neurons / cytology
  • Neurons / metabolism*
  • Phenotype
  • Proteins / genetics*
  • Proteins / metabolism
  • RNA, Messenger / pharmacology
  • Receptors, Notch
  • Sequence Homology, Amino Acid
  • Signal Transduction / genetics*
  • Thymus Gland / cytology
  • Thymus Gland / embryology
  • Thymus Gland / metabolism
  • Tubulin / metabolism
  • Xenopus laevis / embryology
  • Xenopus laevis / genetics
  • Xenopus laevis / metabolism

Substances

  • Carrier Proteins
  • DNA, Complementary
  • DX protein, Drosophila
  • Drosophila Proteins
  • Insect Proteins
  • Membrane Proteins
  • N protein, Drosophila
  • Neural Cell Adhesion Molecules
  • Proteins
  • RNA, Messenger
  • Receptors, Notch
  • Tubulin
  • deltex protein, vertebrate