title: Respiratory and autonomic dysfunction in congenital central hypoventilation syndrome.
abstract: The developmental lineage of the PHOX2B-expressing neurons in the retrotrapezoid nucleus (RTN) has been extensively studied. These cells are thought to function as central respiratory chemoreceptors, i.e., the mechanism by which brain Pco2 regulates breathing. The molecular and cellular basis of central respiratory chemoreception is based on the detection of CO2 via intrinsic proton receptors (TASK-2, GPR4) as well as synaptic input from peripheral chemoreceptors and other brain regions. Murine models of congenital central hypoventilation syndrome designed with PHOX2B mutations have suggested RTN neuron agenesis. In this review, we examine, through human and experimental animal models, how a restricted number of neurons that express the transcription factor PHOX2B play a crucial role in the control of breathing and autonomic regulation.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil; tmoreira@icb.usp.br.
authors.forename: Thiago S
authors.initials: TS
authors.lastname: Moreira
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil; and.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Takakura
authors.affiliation: The Ohio State University, College of Medicine, Department of Pathology, Division of Neuropathology, Columbus, Ohio.
authors.forename: Catherine
authors.initials: C
authors.lastname: Czeisler
authors.affiliation: The Ohio State University, College of Medicine, Department of Pathology, Division of Neuropathology, Columbus, Ohio.
authors.forename: Jose J
authors.initials: JJ
authors.lastname: Otero
mesh_terms: D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000209:etiology* / Q000235:genetics; D002628:Chemoreceptor Cells / Q000502:physiology; D004195:Disease Models, Animal; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007040:Hypoventilation / Q000150:complications / Q000151:congenital* / Q000235:genetics / Q000473:pathology; D008526:Medulla Oblongata / Q000378:metabolism / Q000473:pathology; D012120:Respiration Disorders / Q000209:etiology* / Q000235:genetics; D020182:Sleep Apnea, Central / Q000150:complications* / Q000235:genetics / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; C109220:NBPhox protein; D014157:Transcription Factors
keywords: CCHS; breathing; chemoreflex; ventrolateral medulla