title: PLZF regulates fibroblast growth factor responsiveness and maintenance of neural progenitors.
abstract: Distinct classes of neurons and glial cells in the developing spinal cord arise at specific times and in specific quantities from spatially discrete neural progenitor domains. Thus, adjacent domains can exhibit marked differences in their proliferative potential and timing of differentiation. However, remarkably little is known about the mechanisms that account for this regional control. Here, we show that the transcription factor Promyelocytic Leukemia Zinc Finger (PLZF) plays a critical role shaping patterns of neuronal differentiation by gating the expression of Fibroblast Growth Factor (FGF) Receptor 3 and responsiveness of progenitors to FGFs. PLZF elevation increases FGFR3 expression and STAT3 pathway activity, suppresses neurogenesis, and biases progenitors towards glial cell production. In contrast, PLZF loss reduces FGFR3 levels, leading to premature neuronal differentiation. Together, these findings reveal a novel transcriptional strategy for spatially tuning the responsiveness of distinct neural progenitor groups to broadly distributed mitogenic signals in the embryonic environment.
authors.affiliation: Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America ; Broad Center for Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America ; Molecular Biology Interdepartmental Graduate Program, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America.
authors.forename: Zachary B
authors.initials: ZB
authors.lastname: Gaber
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Butler
authors.forename: Bennett G
authors.initials: BG
authors.lastname: Novitch
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002645:Chickens; D004843:Epistasis, Genetic / Q000187:drug effects; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D006801:Humans; D007395:Interneurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D055495:Neurogenesis / Q000187:drug effects / Q000235:genetics; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; C513267:Zbtb16 protein, mouse; D005346:Fibroblast Growth Factors; D051498:Receptor, Fibroblast Growth Factor, Type 3