Research article

Distinct roles of Hoxa2 and Krox20 in the development of rhythmic neural networks controlling inspiratory depth, respiratory frequency, and jaw opening

Fabrice Chatonnet^1,2 , Ludovic J Wrobel¹ , Valérie Mézières¹ , Massimo Pasqualetti^3,4 , Sébastien Ducret³ , Emmanuel Taillebourg^5,6 , Patrick Charnay⁵ , Filippo M Rijli³ and Jean Champagnat¹

¹  NGI, UPR 2216, Institut de Neurobiologie Alfred Fessard IFR2218, Centre National de la Recherche Scientifique, F-91198 Gif sur Yvette Cedex, France

²  IGFL UMR 5242 CNRS/INRA/UCB/École Normale Supérieure de Lyon, allée d'Italie, 69364 Lyon Cedex 07, France

³  IGBMC, UMR 7104, CNRS/INSERM/ULP/Collège de France, CU de Strasbourg, F-67404 Illkirch Cedex, France

⁴  Laboratori di Biologia Cellulare e dello Sviluppo, Università di Pisa, Via G Carducci, Pisa, Italy

⁵  INSERM, U 784, Ecole Normale Supérieure, rue d'Ulm, 75230 Paris Cedex 05, France

⁶  CEA, Laboratoire de Biochimie et Biophysique des Systèmes Intégrés, 38054 Grenoble, France

author email corresponding author email

Neural Development 2007, 2:19doi:10.1186/1749-8104-2-19

Published:	26 September 2007

Abstract

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.