Col Julien A Dal, Matsuo Tomohiko, Storm Daniel R, Rodriguez Ivan
Department of Zoology and Animal Biology, and NCCR Frontiers in Genetics, University of Geneva, Geneva, Switzerland.
Development. 2007 Jul;134(13):2481-9. doi: 10.1242/dev.006346. Epub 2007 May 30.
The vertebrate olfactory bulb is a remarkably organized neuronal structure, in which hundreds of functionally different sensory inputs are organized into a highly stereotyped topographical map. How this wiring is achieved is not yet understood. Here, we show that the olfactory bulb topographical map is modified in adenylyl cyclase 3 (adenylate cyclase 3)-deficient mice. In these mutants, axonal projection targets corresponding to specific odorant receptors are disorganized, are no longer exclusively innervated by functionally identical axonal projections and shift dramatically along the anteroposterior axis of the olfactory bulb. Moreover, the cyclase depletion leads to the prevention of neuropilin 1 (Nrp1) expression in olfactory sensory neuron axonal projections. Taken together, our data point to a major role played by a crucial element of the odorant-induced transduction cascade, adenylyl cyclase 3, in the targeting of olfactory sensory neuron axons towards the brain. This mechanism probably involves the regulation of receptor genes known to be crucial in axonal guidance processes.
脊椎动物的嗅球是一个结构高度有序的神经元结构，其中数百种功能不同的感觉输入被组织成高度刻板的拓扑图。这种神经连接是如何形成的，目前尚不清楚。在此，我们发现腺苷酸环化酶3（adenylate cyclase 3）基因敲除小鼠的嗅球拓扑图发生了改变。在这些突变体中，对应于特定气味受体的轴突投射靶点变得紊乱，不再仅由功能相同的轴突投射支配，并且沿着嗅球的前后轴发生了显著移位。此外，环化酶的缺失导致嗅觉感觉神经元轴突投射中神经纤毛蛋白1（Nrp1）表达的缺失。综上所述，我们的数据表明，气味诱导转导级联反应的关键元件——腺苷酸环化酶3，在嗅觉感觉神经元轴突向脑内的靶向定位中发挥着重要作用。这种机制可能涉及对已知在轴突导向过程中起关键作用的受体基因的调控。
