Receptor tyrosine phosphatase PTPγ is a regulator of spinal cord neurogenesis.
During spinal cord development the proliferation, migration and survival of neural progenitors and precursors is tightly controlled, generating the fine spatial organisation of the cord. In order to understand better the control of these processes, we have examined the function of an orphan receptor protein tyrosine phosphatase (RPTP) PTPγ, in the developing chick spinal cord. Widespread expression of PTPγ occurs post-embryonic day 3 in the early cord and is consistent with a potential role in either neurogenesis or neuronal maturation. Using gain-of-function and loss-of-function approaches in ovo, we show that PTPγ perturbation significantly reduces progenitor proliferation rates and neuronal precursor numbers, resulting in hypoplasia of the neuroepithelium. PTPγ gain-of-function causes widespread suppression of Wnt/β-catenin-driven TCF signalling. One potential target of PTPγ may therefore be β-catenin itself, since PTPγ can dephosphorylate it in vitro, but alternative targets are also likely. PTPγ loss-of-function is not sufficient to alter TCF signalling. Instead, loss-of-function leads to increased apoptosis and defective cell-cell adhesion in progenitors and precursors. Furthermore, motor neuron precursor migration is specifically defective. PTPγ therefore regulates neurogenesis during a window of spinal cord development, with molecular targets most likely related to Wnt/β-catenin signalling, cell survival and cell adhesion.
UCL Institute of Child Health, University College London, London, UK.
Hamid
H
Hashemi
Michael
M
Hurley
Anna
A
Gibson
Veera
V
Panova
Viktoria
V
Tchetchelnitski
Alastair
A
Barr
Andrew W
AW
Stoker
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002642:Chick Embryo; D018274:Electroporation; D015151:Immunoblotting; D017403:In Situ Hybridization; D009046:Motor Neurons / Q000166:cytology / Q000201:enzymology; D058953:Neural Stem Cells / Q000166:cytology / Q000201:enzymology; D055495:Neurogenesis / Q000502:physiology*; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013116:Spinal Cord / Q000196:embryology* / Q000201:enzymology*; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D051153:Wnt Proteins; D051176:beta Catenin; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5