Regulation of neural precursor differentiation in the embryonic and adult forebrain.
1. Precursors form the neuroepithelium of the developing cortex and also from the adult sub-ventricular zone, can be cloned in vitro after stimulation with fibroblast growth factor (FGF)-2 and have the potential to give rise to both neurons and glia. The generation of neurons from these clones can be stimulated by either a factor derived from an astrocyteprecursor line, Ast-1, or FGF-1. 2. Neuronal differentiation stimulated by FGF-1 can be inhibited by diacylglycerol-lipase inhibitor and mimicked by arachidonic acid, suggesting that the neuronal differentiation is signalled through the PCL gamma pathway. 3. The sequential expression of FGF-2 and FGF-1 within the developing forebrain neuroepithelium fits with the different functions the two FGF play in precursor regulation. 4. We have shown that the precursor response to FGF-1 is regulated by a heparan sulphate proteoglycan (HSPG) expressed within the developing neuroepithelium. Precursors restricted to the astrocyte cell lineage can be stimulated by epidermal growth factor or FGF-2; however, the differentiation into GFAP positive astrocytes appears to require a cytokine acting through the leukaemia inhibitory factor beta receptor.
Bartlett
P F
PF
Walter and Eliza Hall Institute of Medical Research, University of Melbourne, Parkville, Victoria, Australia.
Richards
L R
LR
Kilpatrick
T J
TJ
Talman
P S
PS
Bailey
K A
KA
Brooker
G J
GJ
Dutton
R
R
Koblar
S
S
Nurcombe
V
V
Ford
M
M
D000328:Adult; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D005260:Female; D006801:Humans; D009474:Neurons / Q000502:physiology*; D011247:Pregnancy; D016548:Prosencephalon / Q000196:embryology / Q000254:growth & development* / Q000502:physiology