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Elife. 2015 Oct 12;4. doi: 10.7554/eLife.07834.

Epithelial cells supply Sonic Hedgehog to the perinatal dentate gyrus via transport by platelets.

Choe Y1,2, Huynh T1, Pleasure SJ1,3,4,5.

Author information

1
Department of Neurology, University of California, San Francisco, San Francisco, United States.
2
Department of Neural Development and Disease, Korea Brain Research Institute, Daegu, Republic of Korea.
3
Program in Neuroscience, University of California, San Francisco, San Francisco, United States.
4
Program in Developmental Stem Cell Biology, University of California, San Francisco, San Francisco, United States.
5
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, United States.

Abstract

Dentate neural stem cells produce neurons throughout life in mammals. Sonic hedgehog (Shh) is critical for maintenance of these cells; however, the perinatal source of Shh is enigmatic. In the present study, we examined the role of Shh expressed by hair follicles (HFs) that expand perinatally in temporal concordance with the proliferation of Shh-responding dentate stem cells. Specific inhibition of Shh from HFs or from epithelial sources in general hindered development of Shh-responding dentate stem cells. We also found that the blood-brain barrier (BBB) of the perinatal dentate gyrus (DG) is leaky with stem cells in the dentate exposed to blood-born factors. In attempting to identify how Shh might be transported in blood, we found that platelets contain epithelial Shh, provide Shh to the perinatal DG and that inhibition of platelet generation reduced hedgehog-responsive dentate stem cells.

KEYWORDS:

Shh; dentate gyrus; developmental biology; mouse; neurogenesis; neuroscience; platelet; stem cells

PMID:
26457609
PMCID:
PMC4600762
DOI:
10.7554/eLife.07834
[Indexed for MEDLINE]
Free PMC Article

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