title: Contribution of the Runx1 transcription factor to axonal pathfinding and muscle innervation by hypoglossal motoneurons.
abstract: The runt-related transcription factor Runx1 contributes to cell type specification and axonal targeting projections of the nociceptive dorsal root ganglion neurons. Runx1 is also expressed in the central nervous system, but little is known of its functions in brain development. At mouse embryonic day (E) 17.5, Runx1-positive neurons were detected in the ventrocaudal subdivision of the hypoglossal nucleus. Runx1-positive neurons lacked calcitonin gene-related peptide (CGRP) expression, whereas Runx1-negative neurons expressed CGRP. Expression of CGRP was not changed in Runx1-deficient mice at E17.5, suggesting that Runx1 alone does not suppress CGRP expression. Hypoglossal axon projections to the intrinsic vertical (V) and transverse (T) tongue muscles were sparser in Runx1-deficient mice at E17.5 compared to age-matched wild-type littermates. Concomitantly, vesicular acetylcholine transporter-positive axon terminals and acetylcholine receptor clusters were less dense in the V and T tongue muscles of Runx1-deficient mice. These abnormalities in axonal projection were not caused by a reduction in the total number hypoglossal neurons, failed synaptogenesis, or tongue muscles deficits. Our results implicate Runx1 in the targeting of ventrocaudal hypoglossal axons to specific tongue muscles. However, Runx1 deficiency did not alter neuronal survival or the expression of multiple motoneuron markers as in other neuronal populations. Thus, Runx1 appears to have distinct developmental functions in different brain regions.
authors.affiliation: Division of Anatomical Science, Department of Functional Morphology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi, Tokyo, 173-8610, Japan.|Doctoral Program in Kansei, Behavioral and Brain Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Yoshikawa
authors.affiliation: Doctoral Program in Kansei, Behavioral and Brain Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Hirabayashi
authors.affiliation: Doctoral Program in Kansei, Behavioral and Brain Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Ito
authors.affiliation: Doctoral Program in Kansei, Behavioral and Brain Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ozaki
authors.affiliation: Division of Anatomical Science, Department of Functional Morphology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi, Tokyo, 173-8610, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Aizawa
authors.affiliation: Doctoral Program in Kansei, Behavioral and Brain Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Masuda
authors.affiliation: Doctoral Program in Kansei, Behavioral and Brain Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Senzaki
authors.affiliation: Doctoral Program in Kansei, Behavioral and Brain Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shiga
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002452:Cell Count; D002470:Cell Survival / Q000502:physiology; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism*; D007002:Hypoglossal Nerve / Q000196:embryology* / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D008526:Medulla Oblongata / Q000196:embryology* / Q000473:pathology / Q000503:physiopathology; D018345:Mice, Knockout; D009046:Motor Neurons / Q000473:pathology / Q000502:physiology*; D018482:Muscle, Skeletal / Q000196:embryology / Q000294:innervation* / Q000473:pathology / Q000503:physiopathology; D056347:Neuroanatomical Tract-Tracing Techniques; D009929:Organ Size; D013569:Synapses / Q000502:physiology; D014059:Tongue / Q000196:embryology / Q000294:innervation / Q000473:pathology / Q000503:physiopathology; D050494:Vesicular Acetylcholine Transport Proteins / Q000378:metabolism
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; C493726:Runx1 protein, mouse; D050494:Vesicular Acetylcholine Transport Proteins; D015740:Calcitonin Gene-Related Peptide
keywords: CGRP; Runx; axonal projection; hypoglossal neuron; transcription factor