3' Splicing variants of ret receptor tyrosine kinase are differentially expressed in mouse embryos and in adult mice.

The RET protooncogene encodes for a transmembrane receptor tyrosine kinase and plays a crucial role in nephrogenesis and the enteric nervous system (ENS) development. Alternative splicing at the 3' end of the RET gene generates 3' splicing variants that encode RET 9, RET 51 and RET 43 isoforms. It has been hypothesized that these isoforms perform distinct functions and that their expressions are differentially regulated during mammalian development. To gain an insight into the expression patterns of various ret isoforms during embryogenesis, we investigate the temporal and spatial expressions of ret gene in mouse embryos and in adult mice. We characterized the 3' end of the mouse ret gene and localized the alternatively spliced exons. Using 3' rapid amplification of cDNA ends (3' RACE) and reverse transcription-polymerase chain reaction (RT-PCR), ret 9 and ret 51 transcripts were identified in both mouse embryos and adult mouse tissues. However, the ret 43 transcript was not. Using in situ hybridization, we showed that ret 9 was the dominant ret encoding transcript in mouse embryos. Transcripts of ret 9 were detected in all cranial ganglia; in the sensory and autonomic ganglia of the trunk; in a subset of neurons of the dorsal root ganglion (DRG); in the motor neurons of the spinal cord; in the developing lung and excretory systems; in the enteric neuroblasts of the ENS; and in the thyroid lobes. In contrast, ret 51 expression was weak and restricted to the motor column of the spinal cord, the DRG, the enteric neuroblasts, the lung bud and the kidney. In adult mice, ret 9 expression was relatively widespread in many organs while that of ret 51 was rather restricted. Our data indicated that ret isoforms are temporally and spatially regulated in mouse embryos and adult mouse.