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Distinct roles of Hoxa2 and Krox20 in the development of rhythmic neural networks controlling inspiratory depth, respiratory frequency, and jaw opening
BACKGROUND: Little is known about the involvement of molecular determinants of segmental patterning of rhombomeres (r) in the development of rhythmic neural networks in the mouse hindbrain. Here, we compare the phenotypes of mice carrying targeted inactivations of Hoxa2, the only Hox gene expressed...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2007
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2098766/ https://www.ncbi.nlm.nih.gov/pubmed/17897445 http://dx.doi.org/10.1186/1749-8104-2-19 |
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author | Chatonnet, Fabrice Wrobel, Ludovic J Mézières, Valérie Pasqualetti, Massimo Ducret, Sébastien Taillebourg, Emmanuel Charnay, Patrick Rijli, Filippo M Champagnat, Jean |
author_facet | Chatonnet, Fabrice Wrobel, Ludovic J Mézières, Valérie Pasqualetti, Massimo Ducret, Sébastien Taillebourg, Emmanuel Charnay, Patrick Rijli, Filippo M Champagnat, Jean |
author_sort | Chatonnet, Fabrice |
collection | PubMed |
description | BACKGROUND: Little is known about the involvement of molecular determinants of segmental patterning of rhombomeres (r) in the development of rhythmic neural networks in the mouse hindbrain. Here, we compare the phenotypes of mice carrying targeted inactivations of Hoxa2, the only Hox gene expressed up to r2, and of Krox20, expressed in r3 and r5. We investigated the impact of such mutations on the neural circuits controlling jaw opening and breathing in newborn mice, compatible with Hoxa2-dependent trigeminal defects and direct regulation of Hoxa2 by Krox20 in r3. RESULTS: We found that Hoxa2 mutants displayed an impaired oro-buccal reflex, similarly to Krox20 mutants. In contrast, while Krox20 is required for the development of the rhythm-promoting parafacial respiratory group (pFRG) modulating respiratory frequency, Hoxa2 inactivation did not affect neonatal breathing frequency. Instead, we found that Hoxa2(-/- )but not Krox20(-/- )mutation leads to the elimination of a transient control of the inspiratory amplitude normally occurring during the first hours following birth. Tracing of r2-specific progenies of Hoxa2 expressing cells indicated that the control of inspiratory activity resides in rostral pontine areas and required an intact r2-derived territory. CONCLUSION: Thus, inspiratory shaping and respiratory frequency are under the control of distinct Hox-dependent segmental cues in the mammalian brain. Moreover, these data point to the importance of rhombomere-specific genetic control in the development of modular neural networks in the mammalian hindbrain. |
format | Text |
id | pubmed-2098766 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-20987662007-11-29 Distinct roles of Hoxa2 and Krox20 in the development of rhythmic neural networks controlling inspiratory depth, respiratory frequency, and jaw opening Chatonnet, Fabrice Wrobel, Ludovic J Mézières, Valérie Pasqualetti, Massimo Ducret, Sébastien Taillebourg, Emmanuel Charnay, Patrick Rijli, Filippo M Champagnat, Jean Neural Develop Research Article BACKGROUND: Little is known about the involvement of molecular determinants of segmental patterning of rhombomeres (r) in the development of rhythmic neural networks in the mouse hindbrain. Here, we compare the phenotypes of mice carrying targeted inactivations of Hoxa2, the only Hox gene expressed up to r2, and of Krox20, expressed in r3 and r5. We investigated the impact of such mutations on the neural circuits controlling jaw opening and breathing in newborn mice, compatible with Hoxa2-dependent trigeminal defects and direct regulation of Hoxa2 by Krox20 in r3. RESULTS: We found that Hoxa2 mutants displayed an impaired oro-buccal reflex, similarly to Krox20 mutants. In contrast, while Krox20 is required for the development of the rhythm-promoting parafacial respiratory group (pFRG) modulating respiratory frequency, Hoxa2 inactivation did not affect neonatal breathing frequency. Instead, we found that Hoxa2(-/- )but not Krox20(-/- )mutation leads to the elimination of a transient control of the inspiratory amplitude normally occurring during the first hours following birth. Tracing of r2-specific progenies of Hoxa2 expressing cells indicated that the control of inspiratory activity resides in rostral pontine areas and required an intact r2-derived territory. CONCLUSION: Thus, inspiratory shaping and respiratory frequency are under the control of distinct Hox-dependent segmental cues in the mammalian brain. Moreover, these data point to the importance of rhombomere-specific genetic control in the development of modular neural networks in the mammalian hindbrain. BioMed Central 2007-09-26 /pmc/articles/PMC2098766/ /pubmed/17897445 http://dx.doi.org/10.1186/1749-8104-2-19 Text en Copyright © 2007 Chatonnet et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Chatonnet, Fabrice Wrobel, Ludovic J Mézières, Valérie Pasqualetti, Massimo Ducret, Sébastien Taillebourg, Emmanuel Charnay, Patrick Rijli, Filippo M Champagnat, Jean Distinct roles of Hoxa2 and Krox20 in the development of rhythmic neural networks controlling inspiratory depth, respiratory frequency, and jaw opening |
title | Distinct roles of Hoxa2 and Krox20 in the development of rhythmic neural networks controlling inspiratory depth, respiratory frequency, and jaw opening |
title_full | Distinct roles of Hoxa2 and Krox20 in the development of rhythmic neural networks controlling inspiratory depth, respiratory frequency, and jaw opening |
title_fullStr | Distinct roles of Hoxa2 and Krox20 in the development of rhythmic neural networks controlling inspiratory depth, respiratory frequency, and jaw opening |
title_full_unstemmed | Distinct roles of Hoxa2 and Krox20 in the development of rhythmic neural networks controlling inspiratory depth, respiratory frequency, and jaw opening |
title_short | Distinct roles of Hoxa2 and Krox20 in the development of rhythmic neural networks controlling inspiratory depth, respiratory frequency, and jaw opening |
title_sort | distinct roles of hoxa2 and krox20 in the development of rhythmic neural networks controlling inspiratory depth, respiratory frequency, and jaw opening |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2098766/ https://www.ncbi.nlm.nih.gov/pubmed/17897445 http://dx.doi.org/10.1186/1749-8104-2-19 |
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