Brainstem Respiratory Oscillators Develop Independently of Neuronal Migration Defects in the Wnt/PCP Mouse Mutant looptail

Muriel Thoby-Brisson, Julien Bouvier, Derrick M. Glasco, Michelle E. Stewart, Charlotte Dean, Jennifer N. Murdoch, Jean Champagnat, Gilles Fortin, Anand Chandrasekhar
PLoS ONE. 2012-02-17; 7(2): e31140
DOI: 10.1371/journal.pone.0031140

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1. PLoS One. 2012;7(2):e31140. doi: 10.1371/journal.pone.0031140. Epub 2012 Feb 17.

Brainstem respiratory oscillators develop independently of neuronal migration
defects in the Wnt/PCP mouse mutant looptail.

Thoby-Brisson M(1), Bouvier J, Glasco DM, Stewart ME, Dean C, Murdoch JN,
Champagnat J, Fortin G, Chandrasekhar A.

Author information:
(1)UPR 3294 Neurobiology and Development, CNRS Institute of Neurobiology A.
Fessard, Gif-sur-Yvette, France.

The proper development and maturation of neuronal circuits require precise
migration of component neurons from their birthplace (germinal zone) to their
final positions. Little is known about the effects of aberrant neuronal position
on the functioning of organized neuronal groups, especially in mammals. Here, we
investigated the formation and properties of brainstem respiratory neurons in
looptail (Lp) mutant mice in which facial motor neurons closely apposed to some
respiratory neurons fail to migrate due to loss of function of the Wnt/Planar
Cell Polarity (PCP) protein Vangl2. Using calcium imaging and immunostaining on
embryonic hindbrain preparations, we found that respiratory neurons constituting
the embryonic parafacial oscillator (e-pF) settled at the ventral surface of the
medulla in Vangl2(Lp/+) and Vangl2(Lp/Lp) embryos despite the failure of
tangential migration of its normally adjacent facial motor nucleus. Anatomically,
the e-pF neurons were displaced medially in Lp/+ embryos and rostro-medially
Lp/Lp embryos. Pharmacological treatments showed that the e-pF oscillator
exhibited characteristic network properties in both Lp/+ and Lp/Lp embryos.
Furthermore, using hindbrain slices, we found that the other respiratory
oscillator, the preBötzinger complex, was also anatomically and functionally
established in Lp mutants. Importantly, the displaced e-pF oscillator established
functional connections with the preBötC oscillator in Lp/+ mutants. Our data
highlight the robustness of the developmental processes that assemble the
neuronal networks mediating an essential physiological function.

DOI: 10.1371/journal.pone.0031140
PMCID: PMC3281908
PMID: 22363567 [Indexed for MEDLINE]

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