Defective Respiratory Rhythmogenesis and Loss of Central Chemosensitivity in Phox2b Mutants Targeting Retrotrapezoid Nucleus Neurons
Journal of Neuroscience. 2009-11-25; 29(47): 14836-14846
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1. J Neurosci. 2009 Nov 25;29(47):14836-46. doi: 10.1523/JNEUROSCI.2623-09.2009.
Defective respiratory rhythmogenesis and loss of central chemosensitivity in
Phox2b mutants targeting retrotrapezoid nucleus neurons.
Dubreuil V(1), Thoby-Brisson M, Rallu M, Persson K, Pattyn A, Birchmeier C,
Brunet JF, Fortin G, Goridis C.
(1)Département de Biologie, Ecole normale supérieure, 75005 Paris, France.
The retrotrapezoid nucleus (RTN) is a group of neurons in the rostral medulla,
defined here as Phox2b-, Vglut2-, neurokinin1 receptor-, and Atoh1-expressing
cells in the parafacial region, which have been proposed to function both as
generators of respiratory rhythm and as central respiratory chemoreceptors. The
present study was undertaken to assess these two putative functions using genetic
tools. We generated two conditional Phox2b mutations, which target different
subsets of Phox2b-expressing cells, but have in common a massive depletion of RTN
neurons. In both conditional mutants as well as in the previously described
Phox2b(27Ala) mutants, in which the RTN is also compromised, the respiratory-like
rhythmic activity normally seen in the parafacial region of fetal brainstem
preparations was completely abrogated. Rhythmic motor bursts were recorded from
the phrenic nerve roots in the mutants, but their frequency was markedly reduced.
Both the rhythmic activity in the RTN region and the phrenic nerve discharges
responded to a low pH challenge in control, but not in the mutant embryos.
Together, our results provide genetic evidence for the essential role of the
Phox2b-expressing RTN neurons both in establishing a normal respiratory rhythm
before birth and in providing chemosensory drive.
PMID: 19940179 [Indexed for MEDLINE]