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Technical Report CMS-TR-20070403


Title MicroRNA Profiling of Developing and Regenerating Pancreas Reveal Post-Transcriptional Regulation of Neurogenin3
Author/s Mugdha V. Joglekar, Vishal S. Parekh
National Center for Cell Science, Pune 411007, India


Sameet Mehta
Centre for Modeling and Simulation, Savitribai Phule Pune University, Pune 411 007 India


Ramesh R. Bhonde and Anandwardhan A. Hardikar
National Center for Cell Science, Pune 411007, India
Abstract The mammalian pancreas is known to show a remarkable degree of regenerative ability. Several studies till now have demonstrated that the mammalian pancreas can regenerate in normal as well as diabetic conditions. These studies illustrate that pancreatic transcription factors that are seen to be expressed in a temporal fashion during development are re-expressed during regeneration. The only known exception to this is Neurogenin3 (NGN3). Though NGN3 protein, which marks all the pro-endocrine cells during development, is not seen during pancreas regeneration, functional neo-islets are generated within 4 weeks after 70% pancreatectomy. We observed that pancreatic transcription factors upstream of neurogenin3 (ngn3) showed similar expression patterns during development and regeneration. However, gene transcripts of transcription factors downstream of ngn3 (neuroD and Nkx2.2) did not show such similarities in their expression. Since NGN3 protein was not detected at any time point during regeneration, we reasoned that post-transcriptional gene silencing by microRNAs may be a possible mechanism. We carried out microRNA analysis of 283 known and validated mouse microRNAs during different stages of pancreatic development and regeneration and found several similarities in expression patterns, though specific differences do exist. We identified that 4 microRNAs; miR-15a, miR-15b, miR-16 and miR-195, which can potentially bind to neurogenin3 transcript, are expressed at least 200-fold higher in the regenerating mouse pancreas as compared to embryonic day (e)10.5 or e16.5 developing mouse pancreas. We demonstrate here that increased abundance of microRNAs that can bind to 3’UTR of ngn3, may be responsible for inhibition of translation. These microRNAs thus allow endocrine pancreas regeneration via an alternate pathway that does not involve expression of NGN3 protein. Our studies on microRNA profiling of developing and regenerating pancreas provide us with better understanding of mechanisms that regulate post-natal islet neogenesis.
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Citing This Document Mugdha V. Joglekar, Vishal S. Parekh, Sameet Mehta, Ramesh R. Bhonde, and Anandwardhan A. Hardikar , MicroRNA Profiling of Developing and Regenerating Pancreas Reveal Post-Transcriptional Regulation of Neurogenin3 . Technical Report CMS-TR-20070403 of the Centre for Modeling and Simulation, Savitribai Phule Pune University, Pune 411007, India (2007); available at http://cms.unipune.ac.in/reports/.
Notes, Published Reference, Etc. Accepted for publication in Developmental Biology as:
Mugdha V. Joglekar, Vishal S. Parekh, Sameet Mehta, Ramesh R. Bhonde, and Anandwardhan A. Hardikar , MicroRNA Profiling of Developing and Regenerating Pancreas Reveal Post-Transcriptional Regulation of Neurogenin3 . Developmental Biology (2007).
Contact sameet AT cms.unipune.ac.in
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