@article{a04a7f34f78f438b8f53de697305ace0,
title = "Spatiotemporal Control of CNS Myelination by Oligodendrocyte Programmed Cell Death through the TFEB-PUMA Axis",
abstract = "Nervous system function depends on proper myelination for insulation and critical trophic support for axons. Myelination is tightly regulated spatially and temporally, but how it is controlled molecularly remains largely unknown. Here, we identified key molecular mechanisms governing the regional and temporal specificity of CNS myelination. We show that transcription factor EB (TFEB) is highly expressed by differentiating oligodendrocytes and that its loss causes precocious and ectopic myelination in many parts of the murine brain. TFEB functions cell-autonomously through PUMA induction and Bax-Bak activation to promote programmed cell death of a subset of premyelinating oligodendrocytes, allowing selective elimination of oligodendrocytes in normally unmyelinated brain regions. This pathway is conserved across diverse brain areas and is critical for myelination timing. Our findings define an oligodendrocyte-intrinsic mechanism underlying the spatiotemporal specificity of CNS myelination, shedding light on how myelinating glia sculpt the nervous system during development.",
keywords = "CNS, PUMA, myelination, oligodendrocyte, programmed cell death, stress response, temporal and regional specificity, transcription factor EB",
author = "Sun, {Lu O.} and Mulinyawe, {Sara B.} and Collins, {Hannah Y.} and Adiljan Ibrahim and Qingyun Li and Simon, {David J.} and Marc Tessier-Lavigne and Barres, {Ben A.}",
note = "Funding Information: We thank Drs. Liqun Luo, J. Bradley Zuchero, Steven A. Sloan, and Christopher J. Bohlen for helpful comments on the manuscript. We thank Dr. Onkar Dhande for technical assistance and the members of the Barres and Luo laboratories for assistance and discussions. This work was supported by the Helen Hay Whitney Foundation (to L.O.S.), a National Multiple Sclerosis Society career transition award ( TA-1705-27634 to L.O.S.), an NIH Pathway to Independence award ( 1K99EY029330 to L.O.S.), the Vincent J. Coates Research Foundation (to B.A.B.), the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (to B.A.B), the Myra Reinhard Family Foundation (to B.A.B), NIH RO1 NS089786-05 (to M.T.-L.), the Stanford Neuroscience Microscopy Service ( NIH NS069375 ), the Stanford Cell Sciences Imaging Facility ( NCRR 1S10RR026780 ), and the Stanford Functional Genomic Facility ( NIH S10OD018220 ). L.O.S. is a Helen Hay Whitney postdoctoral fellow. This paper is dedicated to the memory of our wonderful mentor and colleague, Dr. Ben A. Barres, who recently passed away. Funding Information: We thank Drs. Liqun Luo, J. Bradley Zuchero, Steven A. Sloan, and Christopher J. Bohlen for helpful comments on the manuscript. We thank Dr. Onkar Dhande for technical assistance and the members of the Barres and Luo laboratories for assistance and discussions. This work was supported by the Helen Hay Whitney Foundation (to L.O.S.), a National Multiple Sclerosis Society career transition award (TA-1705-27634 to L.O.S.), an NIH Pathway to Independence award (1K99EY029330 to L.O.S.), the Vincent J. Coates Research Foundation (to B.A.B.), the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (to B.A.B), the Myra Reinhard Family Foundation (to B.A.B), NIH RO1 NS089786-05 (to M.T.-L.), the Stanford Neuroscience Microscopy Service (NIH NS069375), the Stanford Cell Sciences Imaging Facility (NCRR 1S10RR026780), and the Stanford Functional Genomic Facility (NIH S10OD018220). L.O.S. is a Helen Hay Whitney postdoctoral fellow. This paper is dedicated to the memory of our wonderful mentor and colleague, Dr. Ben A. Barres, who recently passed away. Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",
year = "2018",
month = dec,
day = "13",
doi = "10.1016/j.cell.2018.10.044",
language = "English",
volume = "175",
pages = "1811--1826.e21",
journal = "Cell",
issn = "0092-8674",
number = "7",
}