DIXDC1 promotes retinoic acid-induced neuronal differentiation and inhibits gliogenesis in P19 cells

Cell Mol Neurobiol. 2009 Feb;29(1):55-67. doi: 10.1007/s10571-008-9295-9. Epub 2008 Jul 16.

Abstract

Human DIXDC1 is a member of Dishevelled-Axin (DIX) domain containing gene family which plays important roles in Wnt signaling and neural development. In this report, we first confirmed that expression of Ccd1, a mouse homologous gene of DIXDC1, was up-regulated in embryonic developing nervous system. Further studies showed that Ccd1 was expressed specifically in neurons and colocalized with early neuronal marker Tuj1. During the aggregation induced by RA and neuronal differentiation of embryonic carcinoma P19 cells, expressions of Ccd1 as well as Wnt-1 and N-cadherin were dramatically increased. Stable overexpression of DIXDC1 in P19 cells promoted the neuronal differentiation. P19 cells overexpressing DIXDC1 but not the control P19 cells could differentiate into Tuj1 positive cells with RA induction for only 2 days. Meanwhile, we also found that overexpression of DIXDC1 facilitated the expression of Wnt1 and bHLHs during aggregation and differentiation, respectively, while inhibited gliogenesis by down-regulating the expression of GFAP in P19 cells. Thus, our finding suggested that DIXDC1 might play an important role during neurogenesis, overexpression of DIXDC1 in embryonic carcinoma P19 cells promoted neuronal differentiation, and inhibited gliogenesis induced by retinoic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects*
  • Cell Line, Tumor
  • Embryonic Development / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Genes, Regulator
  • Glial Fibrillary Acidic Protein / genetics
  • Glial Fibrillary Acidic Protein / metabolism
  • Humans
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mice
  • Microfilament Proteins / metabolism*
  • Neurogenesis / drug effects*
  • Neuroglia / cytology*
  • Neuroglia / drug effects
  • Neurons / cytology*
  • Neurons / drug effects*
  • Tretinoin / pharmacology*

Substances

  • DIXDC1 protein, human
  • Dixdc1 protein, mouse
  • Glial Fibrillary Acidic Protein
  • Intracellular Signaling Peptides and Proteins
  • Microfilament Proteins
  • Tretinoin