Ret & Kidney Development

The Ret gene plays an integral role in kidney development. As is covered in any basic embryology class, the cross-talk between the ureteric bud (destined to become the collecting system of the kidney) and the metanephrogenic mesenchyme (destined to become the renal parencyma and tubules) is a prime example of how reciprocal signals from two distinct tissue types can influence the development of the other. In the case of the kidney, GDNF (glial-derived neurotrophic factor) secreted by the mesenchyme interacts with the Ret receptor, a membrane tyrosine kinase, on the ureteric bud. This interaction is critical for branching morphogenesis, the process by which the kidney serially reiterates in order to create an organ with a million nephrons, as demonstrated by the fact that mice deficient in the Ret gene have a congenital absence of the kidney.

Ret is important other human diseases as well. It is a proto-oncogene, as gain-of-function mutations lead to various forms of multiple endocrine neoplasia (MEN). Loss-of-function mutations in contrast can lead to either Hirschprung's disease (a congenital absence of the enteric nerves) or renal hypoplasia.