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) PTP gamma, in the developing chick spinal cord. Widespread expression of PTP gamma occurs postembryonic 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 gamma perturbation significantly reduces progenitor proliferation rates and neuronal precursor numbers, resulting in hypoplasia of the neuroepithelium. PTP gamma gain-of-function causes widespread suppression of Wnt/beta-catenin-driven TCF signalling. One potential target of PTP gamma may therefore be beta-catenin itself, since PTP gamma can dephosphorylate it in vitro, but alternative targets are also likely. PTP gamma 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 gamma therefore regulates neurogenesis during a window of spinal cord development, with molecular targets most likely related to Wnt/beta-catenin signalling, cell survival and cell adhesion. Crown Copyright (C) 2010 Published by Elsevier Inc. All rights reserved.