title: Runx1 contributes to the functional switching of bone morphogenetic protein 4 (BMP4) from neurite outgrowth promoting to suppressing in dorsal root ganglion.
abstract: The runt-related transcription factor Runx1 regulates cell-type specification and axonal projections of nociceptive dorsal root ganglion (DRG) neurons, whereas bone morphogenetic protein 4 (BMP4) is required for axonal growth during neuronal development. Although Runx1 has been shown to be involved in BMP4 signaling in non-neural tissues, the Runx1 function in BMP4-dependent regulation of neuronal development is unclear. To investigate interactions between Runx1 and BMP4 in neurite outgrowth, we cultured DRGs from wild-type and Runx1-deficient mouse embryos in the presence or absence of BMP4. Neurite outgrowth was decreased in BMP4-treated wild-type DRGs and untreated Runx1-deficient DRGs, suggesting the inhibitory effect of BMP4 and facilitatory effect of Runx1 on neurite outgrowth. In addition, the combination of BMP4 treatment and Runx1 deficiency increased neurite outgrowth, suggesting that Runx1 is required for BMP4-induced suppression of neurite outgrowth and that the loss of Runx1 results in a functional switch of BMP4 from neurite growth suppressing to neurite growth promoting. Both BMP4 treatment and Runx1 deficiency increased calcitonin gene-related peptide (CGRP)-positive neurons, and CGRP expression was not increased by BMP4 treatment in Runx1-deficient mice, suggesting that Runx1 contributes to BMP4-induced CGRP expression in DRG neurons. Thus, Runx1 contributes to BMP4 regulation of neurite outgrowth and CGRP expression in DRG and may control BMP4 functional switching during embryogenesis.
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. Electronic address: yoshikawa.masaaki@nihon-u.ac.jp.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Yoshikawa
authors.affiliation: Department of Neurobiology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, 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: 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: Azusa
authors.initials: A
authors.lastname: Kobayashi
authors.affiliation: Department of Neurobiology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, 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: Kouji
authors.initials: K
authors.lastname: Senzaki
authors.affiliation: Department of Systems Neuroscience, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, 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: 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: Department of Neurobiology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, 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: Takashi
authors.initials: T
authors.lastname: Shiga
mesh_terms: D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016501:Neurites / Q000378:metabolism*; D055495:Neurogenesis
chemical_list: C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D050676:Core Binding Factor Alpha 2 Subunit; C493726:Runx1 protein, mouse; D015740:Calcitonin Gene-Related Peptide
keywords: BMP4; CGRP; Dorsal root ganglion; Neurite outgrowth; Runx; Transcription factor