Teashirt 3 regulates development of neurons involved in both respiratory rhythm and airflow control.
Neonatal breathing in mammals involves multiple neuronal circuits, but its genetic basis remains unclear. Mice deficient for the zinc finger protein Teashirt 3 (TSHZ3) fail to breathe and die at birth. Tshz3 is expressed in multiple areas of the brainstem involved in respiration, including the pre-Bötzinger complex (preBötC), the embryonic parafacial respiratory group (e-pF), and cranial motoneurons that control the upper airways. Tshz3 inactivation led to pronounced cell death of motoneurons in the nucleus ambiguus and induced strong alterations of rhythmogenesis in the e-pF oscillator. In contrast, the preBötC oscillator appeared to be unaffected. These deficits result in impaired upper airway function, abnormal central respiratory rhythm generation, and altered responses to pH changes. Thus, a single gene, Tshz3, controls the development of diverse components of the circuitry required for breathing.
Caubit
Xavier
X
Unité Mixte de Recherche (UMR) 6216, Centre National de la Recherche Scientifique (CNRS), Université de la Méditerranée, Institut de Biologie du Développement de Marseille Luminy, Parc Scientifique de Luminy, Marseille Cedex 9, France. caubit@ibdm.univ-mrs.fr
Thoby-Brisson
Muriel
M
Voituron
Nicolas
N
Filippi
Pierre
P
Bévengut
Michelle
M
Faralli
Hervé
H
Zanella
Sébastien
S
Fortin
Gilles
G
Hilaire
Gérard
G
Fasano
Laurent
L
D000818:Animals; D000831:Animals, Newborn; D001683:Biological Clocks / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D004594:Electrophysiology; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000502:physiology*; D009415:Nerve Net / Q000254:growth & development / Q000378:metabolism*; D012123:Pulmonary Ventilation / Q000502:physiology*; D012119:Respiration; D012125:Respiratory Center / Q000502:physiology; D012249:Rhombencephalon / Q000254:growth & development / Q000378:metabolism*; D018709:Statistics, Nonparametric; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014939:Work of Breathing / Q000502:physiology*
C534111:Teashirt 3 protein, mouse; D014157:Transcription Factors; D002118:Calcium