Seven protein tyrosine phosphatases are differentially expressed in the developing rat brain

Regulation of protein function through tyrosine phosphorylation is critical in the control of many developmental processes, such as cellular proliferation and differentiation. Growing evidence suggests that tyrosine phosphorylation also regulates key events in neural development. Although a large body of data has demonstrated that protein tyrosine kinases play an important role in neural development, much less is known about their counterparts, protein tyrosine phosphatases (PTPases). Using polymerase chain reaction (PCR) with degenerate primers and a neonatal rat cortex cDNA library, we have identified seven PTPases expressed in the developing rat brain. Four of these are transmembrane PTPases: LAR, LRP, RPTP gamma, and CPTP1. Three are nonreceptor PTPases: PTP-1, P19-PTP, and SHP. Northern hybridization analysis demonstrates that only CPTP1 is preferentially expressed in neural tissues, whereas the others are found abundantly in nonneural tissues as well as in the brain. Within the embryonic and early postnatal brain, the seven PTPases have overlapping, yet unique, distributions. For example, LAR mRNA is highly expressed by both proliferating and postmitotic cells in the cerebral cortex at embryonic day 17 and in all layers of the cortex at postnatal day 4. In contrast, RPTP gamma mRNA is expressed by postmitotic neurons in the embryo and predominantly by neurons in the superficial layers of the postnatal cortex. Several of the PTPases examined here are expressed at very high levels in the embryonic cortical plate and postnatal neocortex, including the subplate and subventricular zone. The spatial and temporal regulation of PTPase gene expression suggests that these PTPases have important roles in signal transduction during early neuronal differentiation and neural development.