+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Progenitor cell proliferation in the retina is dependent on Notch-independent Sonic hedgehog/Hes1 activity

Progenitor cell proliferation in the retina is dependent on Notch-independent Sonic hedgehog/Hes1 activity

Journal of Cell Biology 184(1): 101-112

Sonic hedgehog (Shh) is an indispensable, extrinsic cue that regulates progenitor and stem cell behavior in the developing and adult mammalian central nervous system. Here, we investigate the link between the Shh signaling pathway and Hes1, a classical Notch target. We show that Shh-driven stabilization of Hes1 is independent of Notch signaling and requires the Shh effector Gli2. We identify Gli2 as a primary mediator of this response by showing that Gli2 is required for Hh (Hedgehog)-dependent up-regulation of Hes1. We also show using chromatin immunoprecipitation that Gli2 binds to the Hes1 promoter, which suggests that Hes1 is a Hh-dependent direct target of Gli2 signaling. Finally, we show that Shh stimulation of progenitor proliferation and cell diversification requires Gli2 and Hes1 activity. This paper is the first demonstration of the mechanistic and functional link between Shh, Gli, and Hes1 in the regulation of progenitor cell behavior.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 055207311

Download citation: RISBibTeXText

PMID: 19124651

DOI: 10.1083/jcb.200805155

Related references

Progenitor Cell Proliferation in the Retina Is Dependent on Notch-Independent Sonic Hedgehog/Hes1 Activity. The Journal of Cell Biology 184(1): 101-112, 2009

Sonic Hedgehog regulates Hes1 through a novel mechanism that is independent of canonical Notch pathway signalling. Oncogene 27(10): 1489-1500, 2007

Integrative genomic analyses on HES/HEY family: Notch-independent HES1, HES3 transcription in undifferentiated ES cells, and Notch-dependent HES1, HES5, HEY1, HEY2, HEYL transcription in fetal tissues, adult tissues, or cancer. International Journal of Oncology 31(2): 461-466, 2007

Notch target HES1 inhibits B cell proliferation and induces apoptosis through an E2A-independent mechanism. Blood 102(11): 224b, November 16, 2003

Sonic Hedgehog regulates retinal stem/progenitor cell proliferation. Society for Neuroscience Abstract Viewer & Itinerary Planner : Abstract No 29 8, 2003

Sonic hedgehog promotes mouse inner ear progenitor cell proliferation and hair cell generation in vitro. Neuroreport 17(2): 121-124, 2006

Interaction of PACAP with sonic Hedgehog on neural stem cell and oligodendrocyte progenitor proliferation. Journal of Neurochemistry 85(Suppl. 1): 66, 2003

Improvement of neurological recovery and stimulation of neural progenitor cell proliferation by intrathecal administration of Sonic hedgehog. Journal of Neurosurgery 116(5): 1114-1120, 2012

Reactive Oxygen Species Signaling Promotes HIF1α Stabilization in Sonic Hedgehog-Driven Cerebellar Progenitor Cell Proliferation. Molecular and Cellular Biology 2019, 2019

Retinal ganglion cell-derived sonic hedgehog locally controls proliferation and the timing of RGC development in the embryonic mouse retina. Development 132(22): 5103-5113, 2005

Sonic hedgehog signaling coordinates the proliferation and differentiation of neural stem/progenitor cells by regulating cell cycle kinetics during development of the neocortex. Congenital Anomalies 52(2): 72-77, 2012

Green tea epigallocatechin-3-gallate (EGCG) promotes neural progenitor cell proliferation and sonic hedgehog pathway activation during adult hippocampal neurogenesis. Molecular Nutrition and Food Research 56(8): 1292-1303, 2013

Gli1 mediates lung cancer cell proliferation and Sonic Hedgehog-dependent mesenchymal cell activation. Plos One 8(5): E63226, 2013

Sonic hedgehog protein promotes bone marrow-derived endothelial progenitor cell proliferation, migration and VEGF production via PI 3-kinase/Akt signaling pathways. Acta Pharmacologica Sinica 27(6): 685-693, 2006

Proliferation of progenitor cells in the vertebrate CNS is regulated by Sonic hedgehog. Developmental Biology 198(1): 194, June 1, 1998