DEFECTS IN SENSORY AND AUTONOMIC GANGLIA AND ABSENCE OF LOCUS-COERULEUS IN MICE DEFICIENT FOR THE HOMEOBOX GENE PHOX2A

Phox2a is a vertebrate homeodomain protein expressed in subsets of dif ferentiating neurons. Here, we show that it is essential for proper de velopment of the locus coeruleus, a subset of sympathetic and parasymp athetic ganglia and the VIIth, IXth, and Xth cranial sensory ganglia. In the sensory ganglia, we have identified two differentiation blocks in Phox2a(-/-) mice. First, the transient expression of dopamine-beta- hydroxylase in neuroblasts is abolished, providing evidence that Phox2 a controls noradrenergic traits in vivo. Second, the expression of the GDNF receptor subunit Ret is dramatically reduced, and there is a mas sive increase in apoptosis of ganglion cells, which are known to depen d on GDNF in vivo. Therefore, Phox2a appears to regulate conventional differentiation traits and the ability of neurons to respond to essent ial survival factors.