Hashemia, Hamid and Hurley, Michael and Gibson, Anna and Panova, Veera and Tchetchelnitski, Viktoria and Barr, Alastair J. and Stoker, Andrew W. (2011) Receptor tyrosine phosphatase PTP? is a regulator of spinal cord neurogenesis. Molecular and Cellular Neuroscience, 46 (2). pp. 469-482. ISSN 1044-7431Full text not available from this repository.
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) PTP?, in the developing chick spinal cord. Widespread expression of PTP? 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 PTP? perturbation significantly reduces progenitor proliferation rates and neuronal precursor numbers, resulting in hypoplasia of the neuroepithelium. PTP? gain-of-function causes widespread suppression of Wnt/?-catenin-driven TCF signalling. One potential target of PTP? may therefore be ?-catenin itself, since PTP? can dephosphorylate it in vitro, but alternative targets are also likely. PTP? 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. PTP? therefore regulates neurogenesis during a window of spinal cord development, with molecular targets most likely related to Wnt/?-catenin signalling, cell survival and cell adhesion.
|Subjects:||University of Westminster > Science and Technology > Life Sciences, School of (No longer in use)|
|Depositing User:||Rachel Wheelhouse|
|Date Deposited:||20 Jul 2012 15:16|
|Last Modified:||20 Jul 2012 15:16|
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