Chapter 4 - RET Signaling in Ureteric Bud Formation and Branching

Abstract

The ureteric bud (UB) is an epithelial tube that arises from the nephric duct and branches repetitively to give rise to the renal collecting duct system while also generating inductive signals that promote nephrogenesis by surrounding metanephric mesenchyme (MM) cells. Defects in UB growth and branching can lead to renal agenesis, hypodysplasia, and other congenital abnormalities of the kidney and urinary tract. A key signal that promotes UB morphogenesis is glial cell-derived neurotrophic factor (GDNF), a protein secreted by MM cells that signals to UB cells via the rearranged in transformation (RET) receptor tyrosine kinase and the coreceptor GDNF family receptor α1. This chapter presents a short introduction to the process of UB growth and branching and then focuses on the effects of RET pathway mutations on kidney development in mice and humans, the regulation of Gdnf and Ret expression, the signaling pathways and genes that act downstream of RET, cooperation between GDNF and fibroblast growth factor signaling, the role of RET in patterning the UB, and the cellular behaviors by which RET may influence UB formation and branching morphogenesis.