title: miRNAs in newt lens regeneration: specific control of proliferation and evidence for miRNA networking.
abstract: BACKGROUND
  Lens regeneration in adult newts occurs via transdifferentiation of the pigment epithelial cells (PECs) of the dorsal iris. The same source of cells from the ventral iris is not able to undergo this process. In an attempt to understand this restriction we have studied in the past expression patterns of miRNAs. Among several miRNAs we have found that mir-148 shows an up-regulation in the ventral iris, while members of the let-7 family showed down-regulation in dorsal iris during dedifferentiation.
  
  
  RESULTS
  We have performed gain- and loss-of-function experiments of mir-148 and let-7b in an attempt to delineate their function. We find that up-regulation of mir-148 caused significant decrease in the proliferation rates of ventral PECs only, while up-regulation of let-7b affected proliferation of both dorsal and ventral PECs. Neither miRNA was able to affect lens morphogenesis or induction. To further understand how this effect of miRNA up-regulation is mediated we examined global expression of miRNAs after up-regulation of mir148 and let-7b. Interestingly, we identified a novel level of mirRNA regulation, which might indicate that miRNAs are regulated as a network.
  
  
  CONCLUSIONS
  The major conclusion is that different miRNAs can control proliferation in the dorsal or ventral iris possibly by a different mechanism. Of interest is that down-regulation of the let-7 family members has also been documented in other systems undergoing reprogramming, such as in stem cells or oocytes. This might indicate that reprogramming during newt regeneration shares common molecular signatures with reprogramming in stem or germ cells. On the other hand that miRNAs can regulate the levels of other miRNAs is a novel level of regulation, which might provide new insights on their function.
authors: Department of Biology and Center for Tissue Regeneration and Engineering, University of Dayton, Dayton, Ohio, United States of America.
authors: Kenta
authors: K
authors: Nakamura
authors: Nobuyasu
authors: N
authors: Maki
authors: Albert
authors: A
authors: Trinh
authors: Heidi W
authors: HW
authors: Trask
authors: Jiang
authors: J
authors: Gui
authors: Craig R
authors: CR
authors: Tomlinson
authors: Panagiotis A
authors: PA
authors: Tsonis
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D007498:Iris / Q000166:cytology / Q000378:metabolism; D007908:Lens, Crystalline / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D008156:Luciferases / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D010857:Pigment Epithelium of Eye / Q000166:cytology; D012038:Regeneration; D012455:Salamandridae / Q000235:genetics* / Q000502:physiology*; D014162:Transfection
chemical_list: D035683:MicroRNAs; D008156:Luciferases