Morin X, Cremer H, Hirsch M R, Kapur R P, Goridis C, Brunet J F
Institut de Biologie du Développement de Marseille, CNRS/INSERM/Université de la Mediterranée, France.
Neuron. 1997 Mar;18(3):411-23. doi: 10.1016/s0896-6273(00)81242-8.
Phox2a is a vertebrate homeodomain protein expressed in subsets of differentiating neurons. Here, we show that it is essential for proper development of the locus coeruleus, a subset of sympathetic and parasympathetic 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 Phox2a controls noradrenergic traits in vivo. Second, the expression of the GDNF receptor subunit Ret is dramatically reduced, and there is a massive increase in apoptosis of ganglion cells, which are known to depend on GDNF in vivo. Therefore, Phox2a appears to regulate conventional differentiation traits and the ability of neurons to respond to essential survival factors.
Phox2a是一种在分化神经元亚群中表达的脊椎动物同源结构域蛋白。在此，我们表明它对于蓝斑、交感和副交感神经节的一个亚群以及第VII、IX和第X颅感觉神经节的正常发育至关重要。在感觉神经节中，我们在Phox2a基因敲除小鼠中鉴定出两个分化阻滞。首先，神经母细胞中多巴胺-β-羟化酶的瞬时表达被消除，这证明Phox2a在体内控制去甲肾上腺素能特性。其次，胶质细胞源性神经营养因子（GDNF）受体亚基Ret的表达显著降低，并且神经节细胞的凋亡大量增加，已知这些神经节细胞在体内依赖GDNF。因此，Phox2a似乎调节传统的分化特性以及神经元对必需生存因子的反应能力。
