Expression of the RET proto-oncogene in human embryos

The patterns of RET proto-oncogene expression in mouse, rat, and chicken an d the anomalies observed in targeted RET mutants suggest that RET plays a m ajor role in development of mouse enteric nervous system and in kidney orga nogenesis, Here, we report on in situ hybridization studies describing the pattern of RET protooncogene expression during early development of human e mbryos between 23 and 42 days. We show that the RET gene is expressed in th e developing kidney (nephric duct, mesonephric tubules, and ureteric bud), the presumptive enteric neuroblasts of the developing enteric nervous syste m, cranial ganglia (VII+VIII, IX, and X) and in the presumptive motor neuro ns of the spinal cord. Yet, despite the high level of RET gene expression i n the kidney and in the motor neurons of the developing central nervous sys tem in human embryos, only rare cases with renal agenesis have been reporte d in Hirschsprung disease patients, and no clinical evidence of spinal cord involvement has been shown in patients carrying RET germline mutations (i. e., multiple endocrine neoplasia syndromes and Hirschsprung disease). Am. J . Med. Genet, 80:481-486, 1998. (C) 1998 Wiley-Liss, Inc.