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Abstract
Peng Kang,1,6 Hyun Kyoung Lee,1,6 Stacey M. Glasgow,1 Meggie Finley,1 Tataka Donti,2 Zachary B. Gaber,4 Brett H. Graham,2 Aaron E. Foster,1 Bennett G. Novitch,4 Richard M. Gronostajski,5 and Benjamin Deneen1,3,*
1 Center for Cell and Gene Therapy
2 Department of Molecular and Human Genetics
3 Department of Neuroscience
Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
4 Department of Neurobiology and Broad Center for Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine
at UCLA, 610 Charles E Young Dr. East, Los Angeles, CA 90095, USA
5 Developmental Genomics Group, New York State Center of Excellence in Bioinformatics and Life Sciences, Department of Biochemistry
and Program in Neurosciences, State University of New York at Buffalo, Buffalo, NY 14214, USA
6 These authors contributed equally to this work
*Correspondence: Benjamin Deneen
Summary
Transcriptional cascades that operate over the course of lineage development are fundamental mechanisms that control cellular differentiation. In the developing central nervous system (CNS), these mechanisms are well characterized during neurogenesis, but remain poorly defined during neural stem cell commitment to the glial lineage. NFIA is a transcription factor that plays a crucial role in the onset of gliogenesis; we found that its induction is regulated by the transcription factor Sox9 and that this relationship mediates the initiation of gliogenesis. Subsequently, Sox9 and NFIA form a complex and coregulate a set of genes induced after glial initiation. Functional studies revealed that a subset of these genes, Apcdd1 and Mmd2, perform key migratory and metabolic roles during astro-gliogenesis, respectively. In sum, these studies delineate a transcriptional regulatory cascade that operates during the initiation of gliogenesis and identifies a unique set of genes that regulate key aspects of astro-glial precursor physiology during development.
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