Prenatal development of central rhythm generation
Respiratory Physiology & Neurobiology. 2011-08-01; 178(1): 146-155
DOI: 10.1016/j.resp.2011.04.013
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1. Respir Physiol Neurobiol. 2011 Aug 31;178(1):146-55. doi:
10.1016/j.resp.2011.04.013. Epub 2011 Apr 16.
Prenatal development of central rhythm generation.
Champagnat J(1), Morin-Surun MP, Bouvier J, Thoby-Brisson M, Fortin G.
Author information:
(1)Neurobiologie et Développement (UPR 3294, CNRS), Neuro-Sud Paris (IFR 144),
Centre de Recherche de Gif-sur Yvette (CNRS, FRC 3115), Gif-sur-Yvette, France.
Foetal breathing in mice results from prenatal activity of the two coupled
hindbrain oscillators considered to be responsible for respiratory rhythm
generation after birth: the pre-Bötzinger complex (preBötC) is active shortly
before the onset of foetal breathing; the parafacial respiratory group (e-pF in
embryo) starts activity one day earlier. Transcription factors have been
identified that are essential to specify neural progenitors and lineages forming
each of these oscillators during early development of the neural tube: Hoxa1,
Egr2 (Krox20), Phox2b, Lbx1 and Atoh1 for the e-pF; Dbx1 and Evx1 for the preBötC
which eventually grow contralateral axons requiring expression of Robo3.
Inactivation of the genes encoding these factors leads to mis-specification of
these neurons and distinct breathing abnormalities: apneic patterns and loss of
central chemosensitivity for the e-pF (central congenital hypoventilation
syndrome, CCHS, in humans), complete loss of breathing for the preBötC,
right-left desynchronized breathing in Robo3 mutants. Mutations affecting
development in more rostral (pontine) respiratory territories change the shape of
the inspiratory drive without affecting the rhythm. Other (primordial) embryonic
oscillators start in the mouse three days before the e-pF, to generate low
frequency (LF) rhythms that are probably required for activity-dependent
development of neurones at embryonic stages; in the foetus, however, they are
actively silenced to avoid detrimental interaction with the on-going respiratory
rhythm. Altogether, these observations provide a strong support to the previously
proposed hypothesis that the functional organization of the respiratory generator
is specified at early stages of development and is dual in nature, comprising two
serially non-homologous oscillators.
Copyright © 2011 Elsevier B.V. All rights reserved.
DOI: 10.1016/j.resp.2011.04.013
PMID: 21527363 [Indexed for MEDLINE]