Cycles of vascular plexus formation within the nephrogenic zone of the developing mouse kidney

Abstract

The renal vasculature is required for blood filtration, blood pressure regulation, and pH maintenance, as well as other specialised kidney functions. Yet, despite its importance, many aspects of its development are poorly understood. To provide a detailed spatiotemporal analysis of kidney vascularisation, we collected images of embryonic mouse kidneys at various developmental time-points. Here we describe the first stages of kidney vascularisation and demonstrate that polygonal networks of vessels (endothelial plexuses) form in cycles at the periphery of the kidney. We show that kidney vascularisation initiates at E11, when vessels connected to the embryonic circulation form a ring around the ureteric bud. From E13.5, endothelial plexuses organise around populations of cap mesenchymal and ureteric bud cells in a cyclical, predictable manner. Specifically, as the ureteric bud bifurcates, endothelia form across the bifurcation site as the cap mesenchyme splits. The plexuses are vascular, carry erythrocytes, are enclosed within a basement membrane, and can always be traced back to the renal artery. Our results are a major step towards understanding how the global architecture of the renal vasculature is achieved.

Refuting the hypothesis that semaphorin‐3f/neuropilin‐2 exclude blood vessels from the cap mesenchyme in the developing kidney

“…We previously demonstrated that renal endothelia pattern around, but do not enter, the cap mesenchyme in the nephrogenic zone of the developing kidney (Munro et al, 2017) (Fig. 1A).…”

“…Although GUDMAP has little data on renal Sema3f expression prior to E15.5, data from the Allen Brain Atlas (Lein et al, 2007) show that Sema3f is also expressed in the kidney at E11.5 and E13.5 ( Fig. At the earliest stages of renal organogenesis (E10.5-E11.5), the kidney is predominantly avascular, despite being surrounded by blood vessels (Munro et al, 2017). At the earliest stages of renal organogenesis (E10.5-E11.5), the kidney is predominantly avascular, despite being surrounded by blood vessels (Munro et al, 2017).…”

Adaptive self‐organization in the embryo: its importance to adult anatomy and to tissue engineering

“…; Muthukrishnan et al. ) and, when a tip divides and its daughters become separated by new stalk, only the cap cells that surround the diverging tips retain the cap phenotype and the space between them becomes occupied by a newly sprouting blood vessel (Munro, ). Caps do not divide in this way when they are induced chemically in pure mesenchyme (Davies & Garrod, ; Kuure et al.…”

“…). The vessels seem to find themselves there by growing up the stalks of the developing tree (Munro, ). These two facts illustrate something else common in self‐organizing systems: one tissue type, in this case ureteric bud, may be a primary organizer of space, while other entities such as the cap and the blood vessels take their cues from it.…”

“…In the kidney, the tips of growing branches are surrounded by a population of mesenchymal stem cells, the 'cap mesenchyme' (Schreiner, 1902;Reinhoff, 1922). At least in mouse, this population depends on BMP7 and FGF9 signalling from the tip for its continued maintenance (Barak et al 2012;Muthukrishnan et al 2015) and, when a tip divides and its daughters become separated by new stalk, only the cap cells that surround the diverging tips retain the cap phenotype and the space between them becomes occupied by a newly sprouting blood vessel (Munro, 2017). Caps do not divide in this way when they are induced chemically in pure mesenchyme (Davies & Garrod, 1995;Kuure et al 2007).…”