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 Ho
x family precedes rhombomere formation, and analysis of mouse Hox mutations
revealed that they play an important role in the establishment of rhombome
re-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 rhombo
meric pattern of Hox expression has any influence on the establishment of t
he neuronal circuitry of the mature brainstem. The Hoxa1 gene is the earlie
st Hox gene expressed in the developing hindbrain. Moreover, it is rapidly
downregulated. Previous analysis of mouse Hoxa1(-/-) mutants has focused on
early alterations of hindbrain segmentation and patterning. Here, we show
that ectopic neuronal groups in the hindbrain of Hoxa1(-/-) mice establish
a supernumerary neuronal circuit that escapes apoptosis and becomes functio
nal postnatally. This system develops from mutant rhombomere 3 (r3)-r4 leve
ls, includes an ectopic group of progenitors with r2 identity, and integrat
es the rhythm-generating network controlling respiration at birth. This is
the first demonstration that changes in Hox expression patterns allow the s
election of novel neuronal circuits regulating vital adaptive behaviors. Th
e implications for the evolution of brainstem neural networks are discussed
.