Early development of respiratory rhythm generation in mouse and chick.

ABSTRACT

We are investigating neuronal circuits resulting from conservative developmental mechanisms orchestrating the segmentation of the vertebrates hindbrain into compartments called rhombomeres (r). Segmentation transcription factors Hoxa1, Krox20 and kreisler are expressed in the future rhombomeres r4-r5, r3 and r5, r5-r6, respectively. In mice, the in vivo and in vitro analysis of neuronal groups after inactivation of these three genes revealed distinct postnatal respiratory phenotypes associated with defects of central respiratory controls resulting from deletion, neoformation or reconfiguration of modular circuits. In chick and mice, we have found neuronal rhythm generators that conform to the rhombomeric anatomical pattern as early as at the end of the segmentation. By isolating chick hindbrain segments in vitro, we have also identified rhombomeric motifs allowing the formation or deletion of a specific (GABAergic) rhythm-promoting module. Therefore, primordial rhombomeric organization of the hindbrain seems to determine a modular organization of the rhythmogenic network, thereby influencing later function of brainstem respiratory control networks.