Axonal extension and synaptic targeting are usually completed during early development, but the axonal length and synaptic integrity need to be actively maintained during later developmental stages and the adult life. Failure in the axonal length maintenance and the subsequent axonal degeneration have been associated with neurological disorders, but currently little is known about the genetic factors controlling this process. Here, we show that regulated intracellular levels of cAMP-dependent protein kinase A (PKA) are critical for the axon maintenance during the transition from the early to the later larval stages in the Drosophila class IV dendritic arborization (da) sensory neurons. Our data indicate that when the intracellular levels of PKA are increased via genetic manipulations, these peripheral neurons initially form synapses with wild-type appearance, at their predicted ventral nerve cord (VNC) target sites (in the first and second instar larval stages), but that their synapses disintegrate, and the axons retract and become fragmented in the subsequent larval stages (third larval stage). The affected axonal endings at the disintegrated synaptic sites still express the characteristic presynaptic and cytoskeletal markers such as Bruchpilot and Fascin, indicating that the synapse had been initially properly formed, but that it later lost its integrity. Finally, the phenotype is significantly more prominent in the axons of the neurons whose cell bodies are located in the posterior body segments. We propose that the reason for this is the fact that during the larval development the posterior neurons face a much greater challenge while trying to keep up with the fast-paced growth of the larval body, and that PKA is critical for this process. Our data reveal PKA as a novel factor in the axonal length and synapse integrity maintenance in sensory neurons. These results could be of help in understanding neurological disorders characterized by destabilized synapses.

轴突延伸和突触靶向通常在早期发育中完成，但是在后期的发育阶段和成年生活中需要积极维持轴突的长度和突触的完整性。轴突长度维持的失败和随后的轴突变性与神经系统疾病有关，但是目前对控制该过程的遗传因素知之甚少。在这里，我们显示调节的细胞内cAMP依赖性蛋白激酶A（PKA）的水平对于果蝇IV类树突状乔化（da）感觉神经元从早期到后期的幼虫过渡期间的轴突维持至关重要。我们的数据表明，当通过基因操作提高细胞内PKA水平时，这些周围神经元最初在其预计的腹侧神经索（VNC）目标部位（在第一和第二龄幼虫阶段）形成具有野生型外观的突触，但其突触解体，轴突在随后的过程中缩回并破碎。幼虫阶段（第三幼虫阶段）。在分解的突触位点处受影响的轴突末端仍表达特征性突触前和细胞骨架标记，例如Br​​uchpilot和Fascin，表明突触最初已正确形成，但后来失去了完整性。最后，在细胞体位于后体节段的神经元的轴突中，该表型显着更显着。我们认为，其原因是这样的事实，即在幼虫发育期间，后神经元在试图跟上幼虫体的快节奏生长的同时面临着更大的挑战，而PKA对于这一过程至关重要。我们的数据显示，PKA是感觉神经元轴突长度和突触完整性维持中的新因素。这些结果可能有助于理解以突触不稳定为特征的神经系统疾病。