PDGF mediates a neuron-astrocyte interaction in the developing retina.
Astrocytes invade the developing retina from the optic nerve head, over the axons of retinal ganglion cells (RGCs). RGCs express the platelet-derived growth factor A-chain (PDGF-A) and retinal astrocytes the PDGF alpha-receptor (PDGFR alpha), suggesting that PDGF mediates a paracrine interaction between these cells. To test this, we inhibited PDGF signaling in the eye with a neutralizing anti-PDGFR alpha antibody or a soluble extracellular fragment of PDGFR alpha. These treatments inhibited development of the astrocyte network. We also generated transgenic mice that overexpress PDGF-A in RGCs. This resulted in hyperproliferation of astrocytes, which in turn induced excessive vasculogenesis. Thus, PDGF appears to be a link in the chain of cell-cell interactions responsible for matching numbers of neurons, astrocytes, and blood vessels during retinal development.
Fruttiger
M
M
MRC Laboratory for Molecular Cell Biology, University College London, United Kingdom.
Calver
A R
AR
Krüger
W H
WH
Mudhar
H S
HS
Michalovich
D
D
Takakura
N
N
Nishikawa
S
S
Richardson
W D
WD
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D001253:Astrocytes / Q000166:cytology / Q000502:physiology*; D019556:COS Cells; D002450:Cell Communication / Q000502:physiology*; D002455:Cell Division; D051379:Mice; D008822:Mice, Transgenic; D009415:Nerve Net / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D012160:Retina / Q000254:growth & development*; D012171:Retinal Vessels / Q000502:physiology
D010982:Platelet-Derived Growth Factor; C075278:platelet-derived growth factor A; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017479:Receptors, Platelet-Derived Growth Factor