Transcriptional regulation of mouse hypoglossal motor neuron somatotopic map formation

Chen, Xin; Wang, Jae Woong; Salin-Cantegrel, Adèle; Dali, Rola; Stifani, Stefano

doi:10.1007/s00429-015-1160-2

Cited by 6 publications

(12 citation statements)

References 42 publications

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“…Importantly, the number of motor neurons exhibiting lateral or dorsal 12N motor neuron molecular traits is decreased when Runx1 is ectopically expressed in all developing 12N motor neurons. These results suggest that Runx1 acts to specifically promote a 'ventromedial' 12N motor neuron phenotype at the expense of 'ventrolateral' and 'dorsomedial' 12N motor neuron identities (Chen et al 2015).…”

Section: Runx1 Involvement In the Formation Of Motor Circuitsmentioning

confidence: 84%

“…8.1) (Chen et al 2015;Yoshikawa et al 2015). In vivo Runx1 inactivation results in decreased 12N motor neuron axonal projections, and overall reduction of innervation density, to intrinsic protrusor muscles (Yoshikawa et al 2015).…”

Section: Runx1 Involvement In the Formation Of Motor Circuitsmentioning

confidence: 99%

“…Runx1 + neurons include visceral and somatic motor neurons in the murine brainstem and cervical spinal cord (Theriault et al 2004;Stifani et al 2008;Guizard et al 2010;Chen et al 2015;Yoshikawa et al 2015). Runx1 also displays a restricted expression in selected motor neuron subtypes in the chick cervical spinal cord (Dasen et al 2005).…”

Section: Runx1 Involvement In the Formation Of Motor Circuitsmentioning

confidence: 99%

“…Runx1 also displays a restricted expression in selected motor neuron subtypes in the chick cervical spinal cord (Dasen et al 2005). The timing of Runx1 expression does not coincide with motor neuron generation and instead roughly correlates with the time when the Runx1 + motor neurons are acquiring their specific molecular identities, cell body positions and/or axonal innervations (Stifani et al 2008;Chen et al 2015). Consistent with this finding, lack of Runx1 activity in Runx1-deficient mice does not perturb the generation of the somatic motor neurons in which Runx1 would normally be expressed (Stifani et al 2008).…”

Section: Runx1 Involvement In the Formation Of Motor Circuitsmentioning

confidence: 99%

“…8.1) (Chen et al 2015;Yoshikawa et al 2015). Importantly, the number of motor neurons exhibiting lateral or dorsal 12N motor neuron molecular traits is decreased when Runx1 is ectopically expressed in all developing 12N motor neurons.…”

Section: Runx1 Involvement In the Formation Of Motor Circuitsmentioning

confidence: 99%

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Roles of Runx Genes in Nervous System Development

Wang

Stifani

2017

Advances in Experimental Medicine and Biology

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Runt-related (Runx) transcription factors play essential roles during development and adult tissue homeostasis and are responsible for several human diseases. They regulate a variety of biological mechanisms in numerous cell lineages. Recent years have seen significant progress in our understanding of the functions performed by Runx proteins in the developing and postnatal mammalian nervous system. In both central and peripheral nervous systems, Runx1 and Runx3 display remarkably specific expression in mostly non-overlapping groups of postmitotic neurons. In the central nervous system, Runx1 is involved in the development of selected motor neurons controlling neural circuits mediating vital functions such as chewing, swallowing, breathing, and locomotion. In the peripheral nervous system, Runx1 and Runx3 play essential roles during the development of sensory neurons involved in circuits mediating pain, itch, thermal sensation and sense of relative position. Runx1 and Runx3 orchestrate complex gene expression programs controlling neuronal subtype specification and axonal connectivity. Runx1 is also important in the olfactory system, where it regulates the progenitor-to-neuron transition in undifferentiated neural progenitor cells in the olfactory epithelium as well as the proliferation and developmental maturation of specific glial cells termed olfactory ensheathing cells. Moreover, upregulated Runx expression is associated with brain injury and disease. Increasing knowledge of the functions of Runx proteins in the developing and postnatal nervous system is therefore expected to improve our understanding of nervous system development, homeostasis and disease.

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Section: Runx1 Involvement In the Formation Of Motor Circuitsmentioning

confidence: 84%

Section: Runx1 Involvement In the Formation Of Motor Circuitsmentioning

confidence: 99%

Section: Runx1 Involvement In the Formation Of Motor Circuitsmentioning

confidence: 99%

Section: Runx1 Involvement In the Formation Of Motor Circuitsmentioning

confidence: 99%

Section: Runx1 Involvement In the Formation Of Motor Circuitsmentioning

confidence: 99%

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Roles of Runx Genes in Nervous System Development

Wang

Stifani

2017

Advances in Experimental Medicine and Biology

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Single-cell profiling of the human primary motor cortex in ALS and FTLD

Pineda

Lee

Fitzwalter

et al. 2021

Preprint

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Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are two devastating and fatal neurodegenerative conditions. While distinct, they share many clinical, genetic, and pathological characteristics, and both show selective vulnerability of layer 5b extratelencephalic-projecting cortical populations, including Betz cells in ALS and von Economo neurons (VENs) in FTLD. Here, we report the first high resolution single-cell atlas of the human primary motor cortex (MCX) and its transcriptional alterations in ALS and FTLD across ~380,000 nuclei from 64 individuals, including 17 control samples and 47 sporadic and C9orf72-associated ALS and FTLD patient samples. We identify 46 transcriptionally distinct cellular subtypes including two Betz-cell subtypes, and we observe a previously unappreciated molecular similarity between Betz cells and VENs of the prefrontal cortex (PFC) and frontal insula. Many of the dysregulated genes and pathways are shared across excitatory neurons, including stress response, ribosome function, oxidative phosphorylation, synaptic vesicle cycle, endoplasmic reticulum protein processing, and autophagy. Betz cells and SCN4B+ long-range projecting L3/L5 cells are the most transcriptionally affected in both ALS and FTLD. Lastly, we find that the VEN/Betz cell-enriched transcription factor, POU3F1, has altered subcellular localization, co-localizes with TDP-43 aggregates, and may represent a cell type-specific vulnerability factor in the Betz cells of ALS and FTLD patient tissues.

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Diverse physiological properties of hypoglossal motoneurons innervating intrinsic and extrinsic tongue muscles

Wealing

Cholanian

Flanigan

et al. 2019

Journal of Neurophysiology

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The mammalian tongue contains eight muscles that collaborate to ensure that suckling, swallowing, and other critical functions are robust and reliable. Seven of the eight tongue muscles are innervated by hypoglossal motoneurons (XIIMNs). A somatotopic organization of the XII motor nucleus, defined in part by the mechanical action of a neuron’s target muscle, has been described, but whether or not XIIMNs within a compartment are functionally specialized is unsettled. We hypothesize that developing XIIMNs are assigned unique functional properties that reflect the challenges that their target muscle faces upon the transition from in utero to terrestrial life. To address this, we studied XIIMNs that innervate intrinsic and extrinsic tongue muscles, because intrinsic muscles play a more prominent role in suckling than the extrinsic muscles. We injected dextran-rhodamine into the intrinsic longitudinal muscles (IL) and the extrinsic genioglossus, and physiologically characterized the labeled XIIMNs. Consistent with earlier work, IL XIIMNs ( n = 150) were located more dorsally within the nucleus, and GG XIIMNs ( n = 55) more ventrally. Whole cell recordings showed that resting membrane potential was, on average, 9 mV more depolarized in IL than in GG XIIMNs ( P = 0.0019), and the firing threshold in response to current injection was lower in IL (−31 ± 23 pA) than in GG XIIMNs (225 ± 39 pA; P < 0.0001). We also found that the appearance of net outward currents in GG XIIMNs occurred at more hyperpolarized membrane potentials than IL XIIMNs, consistent with lower excitability in GG XIIMNs. These observations document muscle-specific functional specializations among XIIMNs. NEW & NOTEWORTHY The hypoglossal motor nucleus contains motoneurons responsible for innervating one of seven different muscles with notably different biomechanics and patterns of use. Whether or not motoneurons innervating the different muscles also have unique functional properties (e.g., spiking behavior, synaptic physiology) is poorly understood. In this work we show that neonatal hypoglossal motoneurons innervating muscles that shape the tongue (intrinsic longitudinal muscles) have different electrical properties than those innervating the genioglossus, which controls tongue position.

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Transcriptional regulation of mouse hypoglossal motor neuron somatotopic map formation

Cited by 6 publications

References 42 publications

Roles of Runx Genes in Nervous System Development

Roles of Runx Genes in Nervous System Development

Single-cell profiling of the human primary motor cortex in ALS and FTLD

Diverse physiological properties of hypoglossal motoneurons innervating intrinsic and extrinsic tongue muscles

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