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PLoS Biol. 2013 Oct;11(10):e1001676. doi: 10.1371/journal.pbio.1001676. Epub 2013 Oct 8.

PLZF regulates fibroblast growth factor responsiveness and maintenance of neural progenitors.

Author information

1
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.

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.

PMID:
24115909
PMCID:
PMC3792860
DOI:
10.1371/journal.pbio.1001676
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors have declared that no competing interests exist.

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