MRC Centre for Developmental Neurobiology, New Hunt's House, Guy's Campus, King's College, London SE1 1UL, UK.
Dev Biol. 2010 Mar 1;339(1):65-77. doi: 10.1016/j.ydbio.2009.12.016. Epub 2009 Dec 24.
Signaling proteins often control multiple aspects of cell morphogenesis. Yet the mechanisms that govern their pleiotropic behavior are often unclear. Here we show activity levels and timing mechanisms determine distinct aspects of Jun N-terminal kinase (JNK) pathway dependent axonal morphogenesis in Drosophila mushroom body (MB) neurons. In the complete absence of Drosophila JNK (Basket), MB axons fail to stabilize, leading to their subsequent degeneration. However, with a partial loss of Basket (Bsk), or of one of the upstream JNK kinases, Hemipterous or Mkk4, these axons overextend. This suggests that Bsk activity prevents axons from destabilizing, resulting in degeneration and overextension beyond their terminal targets. These distinct phenotypes require different threshold activities involving the convergent action of two distinct JNK kinases. We show that sustained Bsk signals are essential throughout development and act additively but are dispensable at adulthood. We also suggest that graded Bsk inputs are translated into AP-1 transcriptional outputs consisting of Fos and Jun proteins.
信号蛋白通常控制细胞形态发生的多个方面。然而,控制它们多效性行为的机制往往不清楚。在这里,我们展示了活性水平和时间机制决定了果蝇蘑菇体(MB)神经元中 Jun N-末端激酶(JNK)通路依赖性轴突形态发生的不同方面。在完全缺乏果蝇 JNK(Basket)的情况下,MB 轴突无法稳定,导致随后的退化。然而,当 Basket(Bsk)部分缺失,或上游 JNK 激酶 Hemipterous 或 Mkk4 之一缺失时,这些轴突会过度延伸。这表明 Bsk 活性阻止轴突不稳定,导致退化和过度延伸超出其终末靶标。这些不同的表型需要涉及两种不同的 JNK 激酶的会聚作用的不同阈值活性。我们表明,持续的 Bsk 信号在整个发育过程中是必不可少的,并且是相加的,但在成年期是可有可无的。我们还表明,梯度 Bsk 输入被转化为由 Fos 和 Jun 蛋白组成的 AP-1 转录输出。