Transforming growth factor beta signaling functions during mammalian kidney development
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REVIEW
Transforming growth factor beta signaling functions during mammalian kidney development Mihai G. Dumbrava 1 & Jon L. Lacanlale 1,2 & Christopher J. Rowan 1 & Norman D. Rosenblum 1,2,3,4,5 Received: 13 July 2020 / Revised: 22 July 2020 / Accepted: 4 August 2020 # IPNA 2020
Abstract Aberrant transforming growth factor beta (TGFβ) signaling during embryogenesis is implicated in severe congenital abnormalities, including kidney malformations. However, the molecular mechanisms that underlie congenital kidney malformations related to TGFβ signaling remain poorly understood. Here, we review current understanding of the lineage-specific roles of TGFβ signaling during kidney development and how dysregulation of TGFβ signaling contributes to the pathogenesis of kidney malformation. Keywords Transforming growth factor beta . Kidney development . Stroma . Nephron . Ureteric bud
Introduction The mammalian kidney, a bilateral organ, is essential to normal homeostasis via regulation of elements including water, electrolytes, minerals, and acid-base balance as well as extracellular fluid volume and blood pressure (reviewed in [1, 2]). In mammals, the formation of the permanent kidney, the metanephros, is initiated by inductive reciprocal interactions between the nephric duct (ND) and the metanephric mesenchyme (MM), both of which are derived from the intermediate mesoderm (IM). In the mouse, the anterior portion of the IM gives rise to the ND at embryonic day (E) 8.0, whereas the posterior portion forms the MM ([3], reviewed in [4, 5]). Mihai G. Dumbrava and Jon L. Lacanlale contributed equally to this work. * Norman D. Rosenblum [email protected] 1
Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, 686 Bay Street, Toronto M5G 0A4, Canada
2
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto M5S 1A8, Canada
3
Department of Physiology, University of Toronto, Toronto M5S 1A8, Canada
4
Department of Paediatrics, University of Toronto, Toronto M5S 1A8, Canada
5
Division of Nephrology, The Hospital for Sick Children, 555 University Avenue, Toronto M5G 1X8, Canada
Mammalian kidney development begins at E10.5, at which stage reciprocal interactions between the ND and the MM stimulate outgrowth of the ureteric bud (UB) from the ND (reviewed in [2, 6]). Reciprocal inductive interactions between the UB and the MM induce the UB to undergo iterative rounds of branching morphogenesis to ultimately form the renal collecting system which is composed of collecting ducts, calyces, pelvis, and the ureter (reviewed in [6, 7]). Simultaneously, the MM is induced by the UB to condense and differentiate into multipotent nephrogenic and stromal progenitors capable of self-renewal [8–10]. Nephrogenic progenitors undergo mesenchymal-epithelial transition (MET) to form renal vesicles, comma- and S-shaped bodies, and ultimately fully functioning nephrons (reviewed in [11]). Concurrently, stromal progenitors differentiate and give rise to the kidney capsule, vascular pe
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