Effect of p75NTR on the regulation of naturally occurring cell death and retinal ganglion cell number in the mouse eye

Chikako Harada, Takayuki Harada, Kazuaki Nakamura, Yasuo Sakai, Kohichi Tanaka, Luis F. Parada

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Neurotrophins induce neural cell survival and differentiation during retinal development and regeneration through the high-affinity tyrosine kinase (Trk) receptors. On the other hand, nerve growth factor (NGF) binding to the low-affinity neurotrophin receptor p75 (p75NTR) might induce programmed cell death (PCD) in the early phase of retinal development. In the present study, we examined the retinal cell types that experience p75 NTR-induced PCD and identify them to be postmitotic retinal ganglion cells (RGCs). However, retinal morphology, RGC number, and BrdU-positive cell number in p75NTR knockout (KO) mouse were normal after embryonic day 15 (E15). In chick retina, migratory RGCs express p75NTR, whereas layered RGCs express the high-affinity NGF receptor TrkA, which may switch the pro-apoptotic signaling of p75NTR into a neurotrophic one. In contrast to the chick model, migratory RGCs express TrkA, while stratified RGCs express p75NTR in mouse retina. However, RGC number in TrkA KO mouse was also normal at birth. We next examined the expression of transforming growth factor β (TGFβ) receptor, which modulates chick RGC number in combination with p75NTR, but was absent in mouse RGCs. p75 NTR and TrkA seem to be involved in the regulation of mouse RGC number in the early phase of retinal development, but the number may be later adjusted by other molecules. These results suggest the different mechanism of RGC number control between mouse and chick retina.

Original languageEnglish (US)
Pages (from-to)57-65
Number of pages9
JournalDevelopmental Biology
Volume290
Issue number1
DOIs
StatePublished - Feb 1 2006

Keywords

  • Eye development
  • Mouse
  • Neurotrophins
  • Pax6
  • Programmed cell death
  • Retina
  • Retinal ganglion cell
  • TrkA
  • p75

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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