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Transcriptional regulation of mouse hypoglossal motor neuron somatotopic map formation

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Abstract

Somatic motor neurons in the hypoglossal nucleus innervate tongue muscles controlling vital functions such as chewing, swallowing and respiration. Formation of functional hypoglossal nerve circuits depends on the establishment of precise hypoglossal motor neuron maps correlating with specific tongue muscle innervations. Little is known about the molecular mechanisms controlling mammalian hypoglossal motor neuron topographic map formation. Here we show that combinatorial expression of transcription factors Runx1, SCIP and FoxP1 defines separate mouse hypoglossal motor neuron groups with different topological, neurotransmitter and calcium-buffering phenotypes. Runx1 and SCIP are coexpressed in ventromedial hypoglossal motor neurons involved in control of tongue protrusion whereas FoxP1 is expressed in dorsomedial motor neurons associated with tongue retraction. Establishment of separate hypoglossal motor neuron maps depends in part on Runx1-mediated suppression of ventrolateral and dorsomedial motor neuron phenotypes and regulation of FoxP1 expression pattern. These findings suggest that combinatorial actions of Runx1, SCIP and FoxP1 are important for mouse hypoglossal nucleus somatotopic map formation.

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Abbreviations

10N:

Dorsal motor nucleus of vagus

12N:

Hypoglossal nucleus

βGal:

Beta galactosidase

CGRP:

Calcitonin gene related peptide

ENCODE:

Encyclopedia of DNA Elements

HBS:

HEPES-buffered saline

MN:

Motor neuron

PBS:

Phosphate-buffered saline

PNS:

Peripheral nervous system

PV:

Parvalbumin

XGal:

5-Bromo-4-chloro-3-indolyl-β-galactopyranoside

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Acknowledgments

We thank Dr. Silvia Arber for Tau Runx1 mice, Dr. Artur Kania for Hb9 Cre mice, Dr. Jeremy Dasen for anti-SCIP antibodies, and Dr. Jean-Francois Cloutier for microscopy support. We also thank Ye Man Tang and Rita Lo for excellent technical assistance, and Mireille Bouchard-Levasseur and Stephanie Perrino for invaluable help with animal care. X.C. was supported by the National Natural Science Foundation of China (81370029) and the Project of Tianjin Applied Basic and Cutting-edge Technological Research (13JCQNJC10500). A.S.C. was supported by Postdoctoral Fellowship from the Fonds de la Recherche du Québec-Santé. R.D. was supported by CIHR-Vanier Canada Graduate Scholarship. This work was supported by Grants from the Canadian Institutes of Health Research (MOP-123500) and ALS Canada (Bridge Funding) to S.S. who is a James McGill Professor of McGill University.

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Author notes

  1. Xin Chen

    Present address: Department of Neurosurgery, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China

  2. Rola Dali

    Present address: McGill Center for Bioinformatics, McGill University, Montreal, QC, Canada

Authors and Affiliations

  1. Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, Canada

    Xin Chen, Jae Woong Wang, Adele Salin-Cantegrel, Rola Dali & Stefano Stifani

  2. Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China

    Xin Chen

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  1. Xin Chen
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Correspondence to Stefano Stifani.

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X. Chen and J. W. Wang contributed equally.

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Chen, X., Wang, J.W., Salin-Cantegrel, A. et al. Transcriptional regulation of mouse hypoglossal motor neuron somatotopic map formation. Brain Struct Funct 221, 4187–4202 (2016). https://doi.org/10.1007/s00429-015-1160-2

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