@article{6bf632a1d06a44b3be0c77e547797ca7,
title = "Lin28 paralogs regulate lung branching morphogenesis",
abstract = "The molecular mechanisms that govern the choreographed timing of organ development remain poorly understood. Our investigation of the role of the Lin28a and Lin28b paralogs during the developmental process of branching morphogenesis establishes that dysregulation of Lin28a/b leads to abnormal branching morphogenesis in the lung and other tissues. Additionally, we find that the Lin28 paralogs, which regulate post-transcriptional processing of both mRNAs and microRNAs (miRNAs), predominantly control mRNAs during the initial phases of lung organogenesis. Target mRNAs include Sox2, Sox9, and Etv5, which coordinate lung development and differentiation. Moreover, we find that functional interactions between Lin28a and Sox9 are capable of bypassing branching defects in Lin28a/b mutant lungs. Here, we identify Lin28a and Lin28b as regulators of early embryonic lung development, highlighting the importance of the timing of post-transcriptional regulation of both miRNAs and mRNAs at distinct stages of organogenesis.",
keywords = "branching morphogenesis, Lin28a/Lin28b, lung development, post-transcriptional regulation",
author = "Osborne, {Jihan K.} and Kinney, {Melissa A.} and Areum Han and Akinnola, {Kemi E.} and Yermalovich, {Alena V.} and Vo, {Linda T.} and Pearson, {Daniel S.} and Sousa, {Patricia M.} and Sutheera Ratanasirintrawoot and Tsanov, {Kaloyan M.} and Jessica Barragan and North, {Trista E.} and Metzger, {Ross J.} and Daley, {George Q.}",
note = "Funding Information: We would like to thank R. Grant Rowe and Deepak Jha of the Daley lab and members of the Kim lab for constructive reading of the manuscript and Thorsten Schlaeger and Trevor Bingham for help with ImageJ analysis. G.Q.D. was supported by NIH RO1GM107536 and RO1GM107536-03S1 and funds from the Boston Children's Hospital Stem Cell Program.J.K.O. was supported by a post-doctoral T32 Hematology/Oncology Training grant and the Burroughs Wellcome Fund. L.T.V. was supported by the NSF graduate research fellowship. A.V.Y. was supported by NIH F99 CA212487 predoctoral fellowship. K.M.T. was an HHMI International Student Research Fellow and a Herchel Smith Graduate Fellow. J.K.O. and G.Q.D, wrote the manuscript and R.J.M. provided expertise and helped revise the manuscript. J.K.O. K.E.A. L.T.V. A.V.Y. and D.S.P. performed experiments. T.E.N. helped revise the manuscript. S.R. and K.M.T. designed and cloned LIN28A mutants. A.H. and M.A.K. performed RNA-seq and analysis. G.Q.D. holds equity in and receives consulting fees for service on the scientific advisory board of 28/7 Therapeutics, Inc. He holds a patent on technology related to LIN28, and J.K.O. A.V.Y. and G.Q.D. have filed a provisional patent related in part to the current work. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science. While citing references scientifically relevant for this work, we also actively worked to promote gender balance in our reference list. Funding Information: We would like to thank R. Grant Rowe and Deepak Jha of the Daley lab and members of the Kim lab for constructive reading of the manuscript and Thorsten Schlaeger and Trevor Bingham for help with ImageJ analysis. G.Q.D. was supported by NIH RO1GM107536 and RO1GM107536-03S1 and funds from the Boston Children{\textquoteright}s Hospital Stem Cell Program .J.K.O. was supported by a post-doctoral T32 Hematology/Oncology Training grant and the Burroughs Wellcome Fund . L.T.V. was supported by the NSF graduate research fellowship. A.V.Y. was supported by NIH F99 CA212487 predoctoral fellowship. K.M.T. was an HHMI International Student Research Fellow and a Herchel Smith Graduate Fellow . Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = jul,
day = "20",
doi = "10.1016/j.celrep.2021.109408",
language = "English (US)",
volume = "36",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "3",
}