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The Journal of Neuroscience, October 20, 2004, 24(42):9383-9390; doi:10.1523/JNEUROSCI.2408-04.2004

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Development/Plasticity/Repair
Induction of a Parafacial Rhythm Generator by Rhombomere 3 in the Chick Embryo

Ana P. Coutinho,^1 * Caroline Borday,^2 * Jonathan Gilthorpe,¹ Stefan Jungbluth,² Jean Champagnat,² Andrew Lumsden,¹ and Gilles Fortin²

¹Medical Research Council Centre for Developmental Neurobiology, King's College London, Guy's Campus, London SE1 1UL, United Kingdom, and ²Neurobiologie Génétique et Intégrative, Institut Alfred Fessard, Centre National de la Recherche Scientifique, 91198 Gif-sur-Yvette, France

Observations of knock-out mice suggest that breathing at birth requires correct development of a specific hindbrain territory corresponding to rhombomeres (r) 3 and 4. Focusing on this territory, we examined the development of a neuronal rhythm generator in the chick embryo. We show that rhythmic activity in r4 is inducible after developmental stage 10 through interaction with r3. Although the nature of this interaction remains obscure, we find that the expression of Krox20, a segmentation gene responsible for specifying r3 and r5, is sufficient to endow other rhombomeres with the capacity to induce rhythmic activity in r4. Induction is robust, because it can be reproduced with r2 and r6 instead of r4 and with any hindbrain territory that normally expresses Krox20 (r3, r5) or can be forced to do so (r1, r4). Interestingly, the interaction between r4 and r3/r5 that results in rhythm production can only take place through the anterior border of r4, revealing a heretofore unsuspected polarity in individual rhombomeres. The r4 rhythm generator appears to be homologous to a murine respiratory parafacial neuronal system developing in r4 under the control of Krox20 and Hoxa1. These results identify a late role for Krox20 at the onset of neurogenesis.

Key words: central pattern generator; transcription factor; Krox20; rhombencephalon; chick embryo; neurogenesis

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Received June 18, 2004; revised September 7, 2004; accepted September 7, 2004.

This article has been cited by other articles:

				H. Mochida, G. Fortin, J. Champagnat, and J. C. Glover Differential Involvement of Projection Neurons During Emergence of Spontaneous Activity in the Developing Avian Hindbrain J Neurophysiol, February 1, 2009; 101(2): 591 - 602. [Abstract] [Full Text] [PDF]

				P. A. Gray Transcription factors and the genetic organization of brain stem respiratory neurons J Appl Physiol, May 1, 2008; 104(5): 1513 - 1521. [Abstract] [Full Text] [PDF]

				M. Thoby-Brisson, J.-B. Trinh, J. Champagnat, and G. Fortin Emergence of the Pre-Botzinger Respiratory Rhythm Generator in the Mouse Embryo J. Neurosci., April 27, 2005; 25(17): 4307 - 4318. [Abstract] [Full Text] [PDF]

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