Adult neural stem cells in distinct microdomains generate previously unknown interneuron types

Florian T Merkle; Luis C Fuentealba; Timothy A Sanders; Lorenza Magno; Nicoletta Kessaris; Arturo Alvarez-Buylla

doi:10.1038/nn.3610

Adult neural stem cells in distinct microdomains generate previously unknown interneuron types

Nat Neurosci. 2014 Feb;17(2):207-14. doi: 10.1038/nn.3610. Epub 2013 Dec 22.

Authors

Florian T Merkle¹, Luis C Fuentealba², Timothy A Sanders³, Lorenza Magno⁴, Nicoletta Kessaris⁵, Arturo Alvarez-Buylla²

Affiliations

¹ 1] Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. [2] Eli and Edythe Broad Center of Regeneration, Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, California, USA. [3] Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts, USA. [4] Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, USA. [5] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA. [6].
² 1] Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. [2] Eli and Edythe Broad Center of Regeneration, Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, California, USA. [3].
³ 1] Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. [2] Eli and Edythe Broad Center of Regeneration, Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, California, USA.
⁴ 1] Wolfson Institute for Biomedical Research, University College London, Gower Street, London, UK. [2] Department of Cell and Developmental Biology, University College London, Gower Street, London, UK.
⁵ 1] Wolfson Institute for Biomedical Research, University College London, Gower Street, London, UK. [2] Department of Cell and Developmental Biology, University College London, Gower Street, London, UK. [3].

PMID: 24362763
PMCID: PMC4100623
DOI: 10.1038/nn.3610

Abstract

Throughout life, neural stem cells (NSCs) in different domains of the ventricular-subventricular zone (V-SVZ) of the adult rodent brain generate several subtypes of interneurons that regulate the function of the olfactory bulb. The full extent of diversity among adult NSCs and their progeny is not known. Here, we report the generation of at least four previously unknown olfactory bulb interneuron subtypes that are produced in finely patterned progenitor domains in the anterior ventral V-SVZ of both the neonatal and adult mouse brain. Progenitors of these interneurons are responsive to sonic hedgehog and are organized into microdomains that correlate with the expression domains of the Nkx6.2 and Zic family of transcription factors. This work reveals an unexpected degree of complexity in the specification and patterning of NSCs in the postnatal mouse brain.

Publication types

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

MeSH terms

Age Factors
Animals
Cerebral Ventricles / cytology
Cerebral Ventricles / growth & development
Gene Expression Regulation, Developmental / genetics
Gene Expression Regulation, Developmental / physiology
Glial Fibrillary Acidic Protein / genetics
Glial Fibrillary Acidic Protein / metabolism
Green Fluorescent Proteins / genetics
Green Fluorescent Proteins / metabolism
Homeodomain Proteins / genetics
Homeodomain Proteins / metabolism
Interneurons / classification*
Interneurons / physiology*
Kruppel-Like Transcription Factors / metabolism
Membrane Microdomains / physiology*
Mice
Neural Stem Cells / cytology*
Neuroglia / physiology
RNA, Untranslated / metabolism
Transcription Factors / genetics
Transcription Factors / metabolism
Transduction, Genetic
Zinc Finger Protein GLI1

Substances

Gli1 protein, mouse
Glial Fibrillary Acidic Protein
Gt(ROSA)26Sor non-coding RNA, mouse
Homeodomain Proteins
Kruppel-Like Transcription Factors
Nkx6.2 protein, vertebrate
RNA, Untranslated
Transcription Factors
Zic1 protein, mouse
Zinc Finger Protein GLI1
Green Fluorescent Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding