EXPRESSION AND INTERACTIONS OF THE 2 CLOSELY-RELATED HOMEOBOX GENES PHOX2A AND PHOX2B DURING NEUROGENESIS

Recent evidence suggests that specific families of homeodomain transcr iption factors control the generation and survival of distinct neurona l types, We had previously characterized the homeobox gene Phox2a, whi ch is expressed in differentiating neurons of the central and peripher al autonomic nervous system as well as in motor nuclei of the hindbrai n, Targeted deletion of the Phox2a gene affects part of the structures in which it is expressed: the locus coeruleus, visceral sensory and p arasympathetic ganglia and, as we show here, the nuclei of the IIIrd a nd IVth cranial nerves, We now report on the characterization of Phox2 b, a close relative of Phox2a, with an identical homeodomain, Phox2a a nd Phox2b are co-expressed at most sites, therefore suggesting a broad er role for Phox2 genes in the specification of the autonomic nervous system and cranial motor nuclei than revealed by the Phox2a knock-out mice, A detailed analysis of the relative timing of Phox2a and Phox2b expression at various sites suggests positive cross-regulations, which are substantiated by the loss of Phox2b expression in cranial ganglia of Phox2a-deficient mice, In the major part of the rhombencephalon, P hox2b expression precedes that of Phox2a and starts in the proliferati ve neuroepithelium, in a pattern strikingly restricted on the dorsoven tral axis and at rhombomeric borders, This suggests that Phox2b links early patterning events to the differentiation of defined neuronal pop ulations in the hindbrain.