Somatic tetraploidy in specific chick retinal ganglion cells induced by nerve growth factor

Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):109-14. doi: 10.1073/pnas.0906121107. Epub 2009 Dec 14.

Abstract

A subset of neurons in the normal vertebrate nervous system contains double the normal amount of DNA in their nuclei. These neurons are all thought to derive from aberrant mitoses in neuronal precursor cells. Here we show that endogenous NGF induces DNA replication in a subpopulation of differentiating chick retinal ganglion cells that express both the neurotrophin receptor p75 and the E2F1 transcription factor, but that lack the retinoblastoma protein. Many of these neurons avoid G2/M transition and remain alive in the retina as tetraploid cells with large cell somas and extensive dendritic trees, and most of them express beta2 nicotinic acetylcholine receptor subunits, a specific marker of retinal ganglion cells innervating lamina F in the stratum-griseum-et-fibrosum-superficiale of the tectal cortex. Tetraploid neurons were also observed in the adult mouse retina. Thus, a developmental program leading to somatic tetraploidy in specific retinal neurons exists in vertebrates. This program might occur in other vertebrate neurons during normal or pathological situations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cell Cycle / physiology
  • Cell Movement / physiology
  • Cells, Cultured
  • Chick Embryo
  • DNA Replication
  • E2F1 Transcription Factor / genetics
  • E2F1 Transcription Factor / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Nerve Growth Factor / genetics
  • Nerve Growth Factor / metabolism*
  • Neurons / cytology
  • Neurons / physiology
  • Ploidies*
  • Receptor, Nerve Growth Factor / genetics
  • Receptor, Nerve Growth Factor / metabolism
  • Retinal Ganglion Cells / cytology
  • Retinal Ganglion Cells / physiology*
  • Retinoblastoma Protein / genetics
  • Retinoblastoma Protein / metabolism

Substances

  • Brain-Derived Neurotrophic Factor
  • E2F1 Transcription Factor
  • Receptor, Nerve Growth Factor
  • Retinoblastoma Protein
  • Nerve Growth Factor