Effect of p75NTR on the regulation of naturally occurring cell death and retinal ganglion cell number in the mouse eye.
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 (p75(NTR)) 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 p75(NTR) knockout (KO) mouse were normal after embryonic day 15 (E15). In chick retina, migratory RGCs express p75(NTR), whereas layered RGCs express the high-affinity NGF receptor TrkA, which may switch the pro-apoptotic signaling of p75(NTR) into a neurotrophic one. In contrast to the chick model, migratory RGCs express TrkA, while stratified RGCs express p75(NTR) in mouse retina. However, RGC number in TrkA KO mouse was also normal at birth. We next examined the expression of transforming growth factor beta (TGFbeta) receptor, which modulates chick RGC number in combination with p75(NTR), 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.
Harada
Chikako
C
Department of Molecular Neurobiology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo 183-8526, Japan.
Harada
Takayuki
T
Nakamura
Kazuaki
K
Sakai
Yasuo
Y
Tanaka
Kohichi
K
Parada
Luis F
LF
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D049109:Cell Proliferation; D002642:Chick Embryo; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D020932:Nerve Growth Factor / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D020917:Receptor, trkA / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
D020800:Receptor, Nerve Growth Factor; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D020932:Nerve Growth Factor; D020917:Receptor, trkA