Respiratory Physiology & Neurobiology 154 (2006) 37–46 Ontogeny of central rhythm generation in chicks and rodents  Chatonnet F. 1 , Borday C., Wrobel L., Thoby-Brisson M., Fortin G., McLean H., Champagnat J. ∗ UPR 2216, Neurobiologie G´ en´ etique et Integrative, Institut f´ ed´ eratif de Neurobiologie Alfred Fessard, C.N.R.S. 1, Avenue de la terrasse, Gif sur Yvette, 91198 Cedex, France Accepted 1 February 2006 Abstract Recent studies help in understanding how the basic organization of brainstem neuronal circuits along the anterior–posterior (AP) axis is set by the Hox-dependent segmentation of the neural tube in vertebrate embryos. Neonatal respiratory abnormalities in Krox20 −/− , Hoxa1 −/− and kreisler mutant mice indicate the vital role of a para-facial (Krox20-dependent, rhombomere 4-derived) respiratory group, that is distinct from the more caudal rhythm generator called Pre-B ¨ otzinger complex. Embryological studies in the chick suggest homology and conservation of this Krox20-dependent induction of parafacial rhythms in birds and mammals. Calcium imaging in embryo indicate that rhythm generators may derive from different cell lineages within rhombomeres. In mice, the Pre-B¨ otzinger complex is found to be distinct from oscillators producing the earliest neuronal activity, a primordial low-frequency rhythm. In contrast, in chicks, maturation of the parafacial generator is tightly linked to the evolution of this primordial rhythm. It seems therefore that ontogeny of brainstem rhythm generation involves conserved processes specifying distinct AP domains in the neural tube, followed by diverse, lineage-specific regulations allowing the emergence of organized rhythm generators at a given AP level. © 2006 Elsevier B.V. All rights reserved. Keywords: Rhyhthm; Brainstem; Development; Embryo; Rhombomeres; Hox; Krox20; Chick; Mouse  This paper is part of a special issue entitled “Frontiers in Compar- ative Physiology II: Respiratory Rhythm, Pattern and Responses to Environmental Change”, guest edited by W.K. Milsom, F.L. Powell and G.S. Mitchell. ∗ Corresponding author. Tel.: +33 1 69 82 34 06; fax: +33 1 69 82 41 78. E-mail address: jean.champagnat@iaf.cnrs-gif.fr (J. Champagnat). 1 Present address: Cellular and Molecular Biology Department, Karolinska Institutet, 171 77 Stockholm, Sweden. 1. Introduction During development, the assembly of neural cir- cuits that encode animal behaviour results from several mechanisms contributing to generate distinct neuronal cell types in appropriate number and position. Among these mechanisms, regionalization of the neural tube is conserved among vertebrates: it controls cell prolifer- ation and exit from the cell cycle at precise location of the neural tube (Lumsden and Krumlauf, 1996; Tanabe 1569-9048/$ – see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.resp.2006.02.004