α-Tanycytes of the adult hypothalamic third ventricle include distinct populations of FGF-responsive neural progenitors

Nat Commun. 2013;4:2049. doi: 10.1038/ncomms3049.

Abstract

Emerging evidence suggests that new cells, including neurons, can be generated within the adult hypothalamus, suggesting the existence of a local neural stem/progenitor cell niche. Here, we identify α-tanycytes as key components of a hypothalamic niche in the adult mouse. Long-term lineage tracing in vivo using a GLAST::CreER(T2) conditional driver indicates that α-tanycytes are self-renewing cells that constitutively give rise to new tanycytes, astrocytes and sparse numbers of neurons. In vitro studies demonstrate that α-tanycytes, but not β-tanycytes or parenchymal cells, are neurospherogenic. Distinct subpopulations of α-tanycytes exist, amongst which only GFAP-positive dorsal α2-tanycytes possess stem-like neurospherogenic activity. Fgf-10 and Fgf-18 are expressed specifically within ventral tanycyte subpopulations; α-tanycytes require fibroblast growth factor signalling to maintain their proliferation ex vivo and elevated fibroblast growth factor levels lead to enhanced proliferation of α-tanycytes in vivo. Our results suggest that α-tanycytes form the critical component of a hypothalamic stem cell niche, and that local fibroblast growth factor signalling governs their proliferation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Animals
  • Cell Proliferation / drug effects
  • Ependymoglial Cells / cytology
  • Ependymoglial Cells / drug effects
  • Ependymoglial Cells / metabolism*
  • Epidermal Growth Factor / pharmacology
  • Excitatory Amino Acid Transporter 1 / metabolism
  • Fibroblast Growth Factor 10 / metabolism*
  • Fibroblast Growth Factors / metabolism*
  • Glial Fibrillary Acidic Protein / metabolism
  • Hypothalamus / cytology*
  • Immunohistochemistry
  • Integrases / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Neural Stem Cells / cytology
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / metabolism*
  • Neuroglia / cytology
  • Neuroglia / drug effects
  • Neuroglia / metabolism
  • Signal Transduction / drug effects
  • Spheroids, Cellular / cytology
  • Spheroids, Cellular / drug effects
  • Spheroids, Cellular / metabolism
  • Third Ventricle / cytology*

Substances

  • Excitatory Amino Acid Transporter 1
  • Fgf10 protein, mouse
  • Fibroblast Growth Factor 10
  • Glial Fibrillary Acidic Protein
  • Slc1a3 protein, mouse
  • fibroblast growth factor 18
  • Fibroblast Growth Factors
  • Epidermal Growth Factor
  • Cre recombinase
  • Integrases