Induction of protein tyrosine phosphatase epsilon transcripts during NGF-induced neuronal differentiation of PC12D cells and during the development of the cerebellum.

ABSTRACT

We have investigated a possible role played by protein tyrosine phosphatase epsilon (PTPepsilon), which was recently cloned and predominantly expressed in brain, in neural differentiation and function. During neuronal cell differentiation of PC12D cells triggered by NGF or FGF, PTPepsilon transcripts were transiently induced at a time between the appearance of transcripts for immediate-early genes and for neuronal cell-specific markers. PTPepsilon was the only PTPase whose transcripts were induced during PC12D cell differentiation among over two dozen PTPase transcripts so far examined. Moreover, in situ hybridization revealed that PTPepsilon transcripts were detected in the neural tube of day 12 postcoitum embryo, and in the nervous system including brain, spinal cord, and ganglions in a ubiquitous manner in late gestational stages. In 4-day-old neonatal mice, the transcripts were widely distributed in the central nervous system where the strongest expression was detected in the hippocampus, cerebral cortex, and olfactory bulb. Interestingly, in day 7 and 16 neonatal brains, the strongest PTPepsilon gene expression was localized in the granular cells of cerebellum, which might indicate that PTPepsilon is involved in the differentiation of the granular cells. The biological significance of PTPepsilon in neuronal differentiation and brain functions is discussed.