MicroRNAs are critical regulators of tuberous sclerosis complex and mTORC1 activity in the size control of the Xenopus kidney

Abstract

Significance The kidney is an essential organ to remove metabolic waste products and retain essential nutrients. To successfully execute these processes, the kidney and its functional unit, the nephron, must be correctly proportioned. Surprisingly, little is known about the processes governing kidney size. Here, we use the amphibian pronephric kidney as a paradigm to study the molecular mechanisms regulating size control. We show for the first time, to our knowledge, that growth factors belonging to the Insulin growth factor family are critically important in establishing kidney size. Moreover, we demonstrate that the strength of the signal is dependent on the presence of small noncoding RNAs termed microRNAs. These provide robustness to size control and ascertain that the kidney develops properly.

Sterol carrier protein 2 regulates proximal tubule size in the Xenopus pronephric kidney by modulating lipid rafts

“…shortened proximal tubules) is highly reminiscent to two recent reports by our group (Zhang et al, 2013; Romaker et al, 2014). Indeed, we believe that all three phenotypes are interconnected.…”

“…Uninjected control embryos increased their proximal tubules from approximately 50 cells at stage 34 to about 230 cells at stage 40, and 320 cells at stage 42 (Fig. 3W) (Romaker et al, 2014). However, scp2 morphants showed little growth and the proximal tubules consisted in average of 110 cells both at stage 40 and 42.…”

“…We incubated embryos with the HRP- or FITC-conjugated B subunit of cholera toxin (CT-B), which specifically binds to GM1 (Holmgren, 1973; Fishman, 1982). Embryos were co-labeled with the 3G8 antibody (Vize et al, 1995) or Erythrina Cristagalli Lectin [ECL, (Romaker et al, 2014)] to visualize the kidney proximal tubules. Pronephroi were dissected and imaged as whole mounts using 2-photon microscopy.…”

“…Indeed, we believe that all three phenotypes are interconnected. Zhang et al (2013) described that changes in cAMP levels cause increased endocytosis and decreased exocytosis, while Romaker et al (2014) identified the role of Insulin and Igf2 in promoting proximal tubule growth. Insulin receptor signaling is well characterized (Pike, 2005; Taniguchi et al, 2006).…”

Compensatory renal hypertrophy following nephrectomy: When and how?

“…Moreover, it was shown in the same Xenopus model that miRNAs have an essential role in regulating tuberous sclerosis complex and mTORC1 activity in kidney size control, which is driven by insulin growth factor family molecules. In particular, insulin and IGF2 were implicated, whose signal strength is regulated by miRNA …”