Generation of the podocyte and tubular components of an amniote kidney: timing of specification and a role for Wnt signaling.

ABSTRACT

Kidneys remove unwanted substances from the body and regulate the internal body environment. These functions are carried out by specialized cells (podocytes) that act as a filtration barrier between the internal milieu and the outside world, and by a series of tubules and ducts that process the filtrate and convey it to the outside. In the kidneys of amniote vertebrates, the filtration (podocyte) and tubular functions are tightly integrated into functional units called nephrons. The specification of the podocyte and tubular components of amniote nephrons is currently not well understood. The present study investigates podocyte and tubule differentiation in the avian mesonephric kidney, and presents several findings that refine our understanding of the initial events of nephron formation. First, well before the first morphological or molecular signs of nephron formation, mesonephric mesenchyme can be separated on the basis of morphology and the expression of the transcription factor Pod1 into dorsal and ventral components, which can independently differentiate in culture along tubule and podocyte pathways, respectively. Second, canonical Wnt signals, which are found in the nephric duct adjacent to the dorsal mesonephric mesenchyme and later in portions of the differentiating nephron, strongly inhibit podocyte but not tubule differentiation, suggesting that Wnt signaling plays an important role in the segmentation of the mesonephric mesenchyme into tubular and glomerular segments. The results are discussed in terms of their broader implications for models of nephron segmentation.