Branching morphogenesis as a driver of renal development

Abstract

Branching morphogenesis is an integral developmental mechanism central to the formation of a range of organs including the kidney, lung, pancreas and mammary gland. The ramified networks of epithelial tubules it establishes are critical for the processes of secretion, excretion and exchange mediated by these tissues. In the kidney, branching serves to establish the collecting duct system that transports urine from the nephrons into the renal pelvis, ureter and finally the bladder. Generally speaking, the formation of these networks in different organs begins with the specification and differentiation of simple bud‐like organ anlage, which then undergo a process of elaboration, typically by bifurcation. This process is often governed by the interaction of progenitor cells at the tips of the epithelia with neighboring mesenchymal cell populations which direct the branching process and which often themselves differentiate to form part of the adult organ. In the kidney, the tips of ureteric bud elaborate through a dynamic cell signaling relationship with overlying nephron progenitor cell populations. These cells sequentially commit to differentiation and the resulting nephrons reintegrate with the ureteric epithelium as development progresses. This review will describe recent advances in understanding the how the elaboration of the ureteric bud is patterned and consider the extent to which this process is shared with other organs.

Biomechanical regulation of cell shapes promotes branching morphogenesis of the ureteric bud epithelium

“…In contrast, the volume range was comparable between the epithelial cells in BI tips and BC ampulla/T-bud stage tips (50-500µm 3 ). To avoid bias arising from volume range differences for initial bud and asymmetrical ampulla stages, the comparisons to BI tips were done within the common cell volume range of 50-297µm 3 for initial bud and 50-272µm 3 for asymmetric ampulla stage (Fig. 7).…”

CRLF1 and CLCF1 in Development, Health and Disease

“…Afterwards, the UB secretes signals that induce the MM to condense around the growing UB tip, forming the cap mesenchyme (CM). At this stage begins CMguided UB branching morphogenesis that occurs rapidly until mid-gestation and slows down after E15.5 [70,71]. Gene expression studies conducted in mice for the identification of such signals found that one of the genes that were highly specific to the UB tip was Crlf1 [72][73][74] with strong expression in mouse (E15.5) and humans (week 15-16; [75]).…”

The Biological Significance and Implications of Planar Cell Polarity for Nephrology

“…Each tip is capped by condensing mesenchyme: the cap mesenchyme, which gives rise to all segments of the nephron. The ureteric bud branches stereotypically in a process termed branching morphogenesis; forming ∼3,000 tips by the end of mouse kidney development (Short and Smyth, 2020) and generating the renal pelvis and collecting duct network. During early renal development, Celsr1-3 transcripts have been localised to the ureteric bud by in situ hybridisation (Shima et al, 2002).…”