title: The H3K27 demethylase JMJD3 is required for maintenance of the embryonic respiratory neuronal network, neonatal breathing, and survival.
abstract: JMJD3 (KDM6B) antagonizes Polycomb silencing by demethylating lysine 27 on histone H3. The interplay of methyltransferases and demethylases at this residue is thought to underlie critical cell fate transitions, and the dynamics of H3K27me3 during neurogenesis posited for JMJD3 a critical role in the acquisition of neural fate. Despite evidence of its involvement in early neural commitment, however, its role in the emergence and maturation of the mammalian CNS remains unknown. Here, we inactivated Jmjd3 in the mouse and found that its loss causes perinatal lethality with the complete and selective disruption of the pre-Bötzinger complex (PBC), the pacemaker of the respiratory rhythm generator. Through genetic and electrophysiological approaches, we show that the enzymatic activity of JMJD3 is selectively required for the maintenance of the PBC and controls critical regulators of PBC activity, uncovering an unanticipated role of this enzyme in the late structuring and function of neuronal networks.
authors.affiliation: European Institute of Oncology (IEO), IFOM-IEO Campus, Via Adamello 16, 20139 Milan, Italy.
authors.forename: Thomas
authors.initials: T
authors.lastname: Burgold
authors.forename: Nicolas
authors.initials: N
authors.lastname: Voituron
authors.forename: Marieta
authors.initials: M
authors.lastname: Caganova
authors.forename: Prem Prakash
authors.initials: PP
authors.lastname: Tripathi
authors.forename: Clement
authors.initials: C
authors.lastname: Menuet
authors.forename: Betsabeh Khoramian
authors.initials: BK
authors.lastname: Tusi
authors.forename: Fabio
authors.initials: F
authors.lastname: Spreafico
authors.forename: Michelle
authors.initials: M
authors.lastname: Bévengut
authors.forename: Christian
authors.initials: C
authors.lastname: Gestreau
authors.forename: Serena
authors.initials: S
authors.lastname: Buontempo
authors.forename: Antonio
authors.initials: A
authors.lastname: Simeone
authors.forename: Laurens
authors.initials: L
authors.lastname: Kruidenier
authors.forename: Gioacchino
authors.initials: G
authors.lastname: Natoli
authors.forename: Stefano
authors.initials: S
authors.lastname: Casola
authors.forename: Gérard
authors.initials: G
authors.lastname: Hilaire
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Testa
mesh_terms: D000818:Animals; D002460:Cell Line; D004622:Embryo, Mammalian / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D056484:Jumonji Domain-Containing Histone Demethylases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism*; D054238:Perinatal Mortality; D016897:Respiratory Burst / Q000502:physiology; D012131:Respiratory Insufficiency / Q000473:pathology; D013004:Somatostatin / Q000378:metabolism
chemical_list: D006657:Histones; D013004:Somatostatin; D056484:Jumonji Domain-Containing Histone Demethylases; C523761:Kdm6b protein, mouse