Xrx1 controls proliferation and multipotency of retinal progenitors

Mol Cell Neurosci. 2003 Jan;22(1):25-36. doi: 10.1016/s1044-7431(02)00025-8.

Abstract

We investigated the function of Xrx1 during Xenopus retinogenesis. Xrx1 overexpression lengthens mitotic activity and ectopically activates the expression of markers of undifferentiated progenitors in the developing retina. We assayed Xrx1 ability to support proliferation with a cell-autonomous mechanism by in vivo lipofection of single retinal progenitors. Xrx1 overexpression increases clonal proliferation while Xrx1 functional inactivation exerts the opposite effect. We also compared the effects of Xrx1 with those of the cyclin-dependent kinase cdk2, a strong mitotic promoter. Despite the similar increase in clonal proliferation displayed by both factors, Xrx1 and cdk2 act differently on retinal cell fate determination. cdk2/cyclinA2 lipofected retinas show a decrease in early-born cell types as ganglion cells and cones and an increase in late-born types such as bipolar neurons. On the contrary, Xrx1 lipofected retinas show no changes in the proportions of the different cell types, thus suggesting a role in supporting multipotency of retinal progenitors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amacrine Cells / cytology
  • Amacrine Cells / metabolism
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • CDC2-CDC28 Kinases*
  • Cell Differentiation / physiology*
  • Cell Division / physiology*
  • Cell Lineage / genetics
  • Cells, Cultured
  • Clone Cells / cytology
  • Clone Cells / metabolism
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases / genetics
  • Cyclin-Dependent Kinases / metabolism
  • Embryo, Nonmammalian
  • Eye Proteins / genetics
  • Eye Proteins / metabolism
  • Gene Expression Regulation, Developmental / genetics*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Multipotent Stem Cells / cytology
  • Multipotent Stem Cells / metabolism*
  • Neuroglia / cytology
  • Neuroglia / metabolism
  • Neurons / cytology
  • Neurons / metabolism*
  • Photoreceptor Cells / cytology
  • Photoreceptor Cells / embryology
  • Photoreceptor Cells / metabolism
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Recombinant Fusion Proteins
  • Retina / cytology
  • Retina / embryology*
  • Retina / metabolism
  • Retinal Ganglion Cells / cytology
  • Retinal Ganglion Cells / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Xenopus Proteins*
  • Xenopus laevis

Substances

  • ATOH7 protein, Xenopus
  • Basic Helix-Loop-Helix Transcription Factors
  • Eye Proteins
  • Homeodomain Proteins
  • Rax protein, Xenopus
  • Recombinant Fusion Proteins
  • Transcription Factors
  • Xenopus Proteins
  • Cyclin D1
  • Protein Serine-Threonine Kinases
  • CDC2-CDC28 Kinases
  • Cdk2 protein, Xenopus
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases