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Neuron. 2017 May 3;94(3):500-516.e9. doi: 10.1016/j.neuron.2017.04.018.

Migrating Interneurons Secrete Fractalkine to Promote Oligodendrocyte Formation in the Developing Mammalian Brain.

Author information

1
Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON M5G 1L7, Canada.
2
Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON M5G 1L7, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5G 1A8, Canada.
3
Regenerative Medicine Program, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON K1H 8L6, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8L6, Canada.
4
Regenerative Medicine Program, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON K1H 8L6, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8L6, Canada; Brain and Mind Research Institute, University of Ottawa, Ottawa, ON K1H 8L6, Canada.
5
Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON M5G 1L7, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5G 1A8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1A8, Canada.
6
Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON M5G 1L7, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5G 1A8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1A8, Canada; Department of Physiology, University of Toronto, Toronto, ON M5G 1A8, Canada. Electronic address: fredam@sickkids.ca.

Abstract

During development, newborn interneurons migrate throughout the embryonic brain. Here, we provide evidence that these interneurons act in a paracrine fashion to regulate developmental oligodendrocyte formation. Specifically, we show that medial ganglionic eminence (MGE) interneurons secrete factors that promote genesis of oligodendrocytes from glially biased cortical precursors in culture. Moreover, when MGE interneurons are genetically ablated in vivo prior to their migration, this causes a deficit in cortical oligodendrogenesis. Modeling of the interneuron-precursor paracrine interaction using transcriptome data identifies the cytokine fractalkine as responsible for the pro-oligodendrocyte effect in culture. This paracrine interaction is important in vivo, since knockdown of the fractalkine receptor CX3CR1 in embryonic cortical precursors, or constitutive knockout of CX3CR1, causes decreased numbers of oligodendrocyte progenitor cells (OPCs) and oligodendrocytes in the postnatal cortex. Thus, in addition to their role in regulating neuronal excitability, interneurons act in a paracrine fashion to promote the developmental genesis of oligodendrocytes.

KEYWORDS:

Neural development; fractalkine; interneurons; neural stem cell; oligodendrocytes

PMID:
28472653
DOI:
10.1016/j.neuron.2017.04.018
[Indexed for MEDLINE]
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