PT  - JOURNAL ARTICLE
AU  - del Toro, Eduardo  Domı́nguez
AU  - Borday, Véronique
AU  - Davenne, Marc
AU  - Neun, Rüdiger
AU  - Rijli, Filippo M.
AU  - Champagnat, Jean
TI  - Generation of a Novel Functional Neuronal Circuit in<em>Hoxa1</em>  Mutant Mice
AID  - 10.1523/JNEUROSCI.21-15-05637.2001
DP  - 2001 Aug 01
TA  - The Journal of Neuroscience
PG  - 5637--5642
VI  - 21
IP  - 15
4099  - http://www.jneurosci.org/content/21/15/5637.short
4100  - http://www.jneurosci.org/content/21/15/5637.full
SO  - J. Neurosci.2001 Aug 01; 21
AB  - Early organization of the vertebrate brainstem is characterized by cellular segmentation into compartments, the rhombomeres, which follow a metameric pattern of neuronal development. Expression of the homeobox genes of the Hox family precedes rhombomere formation, and analysis of mouse Hox mutations revealed that they play an important role in the establishment of rhombomere-specific neuronal patterns. However, segmentation is a transient feature, and a dramatic reconfiguration of neurons and synapses takes place during fetal and postnatal stages. Thus, it is not clear whether the early rhombomeric pattern of Hoxexpression has any influence on the establishment of the neuronal circuitry of the mature brainstem. The Hoxa1 gene is the earliest Hox gene expressed in the developing hindbrain. Moreover, it is rapidly downregulated. Previous analysis of mouseHoxa1−/− mutants has focused on early alterations of hindbrain segmentation and patterning. Here, we show that ectopic neuronal groups in the hindbrain ofHoxa1−/− mice establish a supernumerary neuronal circuit that escapes apoptosis and becomes functional postnatally. This system develops from mutant rhombomere 3 (r3)-r4 levels, includes an ectopic group of progenitors with r2 identity, and integrates the rhythm-generating network controlling respiration at birth. This is the first demonstration that changes inHox expression patterns allow the selection of novel neuronal circuits regulating vital adaptive behaviors. The implications for the evolution of brainstem neural networks are discussed.