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

Notch signaling plays an important role in cell-fate specification in multi cellular organisms by regulating cell-cell communication. The Drosophila de ltex gene encodes a modulator of the Notch pathway that has been shown to i nteract physically with the Ankyrin repeats of Notch. We isolated four dist inct cDNAs corresponding to mouse homologs of deltex - mouse Deltex1 (MDTX1 ), mouse Deltex2 (MDTX2), mouse Deltex2 DeltaE (MDTX2 DeltaE), and mouse De ltex3 (MDTX3). Deduced amino acid sequences of these four cDNAs showed a hi gh degree of similarity to Drosophila Deltex and its human homolog, DTX1 th roughout their lengths, even though they possess distinct structural featur es. MDTX proteins formed homotypic and heterotypic multimers. We found that these genes were expressed in the central, peripheral nervous system and i n the thymus, overlapping with those of mouse Notch1. In mammalian tissue c ulture cells, overexpression of any of the four mouse deltex homologs suppr essed the transcriptional activity of E47, a basic helix-loop-helix (bHLH) protein: in a manner similar to suppression by an activated form of human N otch1 or human DTX1. In addition, overexpression of MDTX2 and MDTX2 DeltaE in C2C12 cells under differentiation-inducing conditions suppressed the exp ression 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 embry os resulted in an expansion of the region expressing the neural cell adhesi on molecule (N-CAM) gene, a marker for the neuroepithelium. Collectively, o ur results suggest that these mouse deltex homologs are involved in vertebr ate Notch signaling and regulation of neurogenesis. (C) 2001 ISDN. Publishe d by Elsevier Science Ltd. All rights reserved.