Neuronal Patterning and Connectivity laboratory, Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf, Falkenried 94, 20251, Hamburg, Germany.
Neuronal Development laboratory, Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf, Falkenried 94, 20251, Hamburg, Germany.
Nat Commun. 2019 Aug 5;10(1):3506. doi: 10.1038/s41467-019-11408-1.
Sensory circuits are typically established during early development, yet how circuit specificity and function are maintained during organismal growth has not been elucidated. To gain insight we quantitatively investigated synaptic growth and connectivity in the Drosophila nociceptive network during larval development. We show that connectivity between primary nociceptors and their downstream neurons scales with animal size. We further identified the conserved Ste20-like kinase Tao as a negative regulator of synaptic growth required for maintenance of circuit specificity and connectivity. Loss of Tao kinase resulted in exuberant postsynaptic specializations and aberrant connectivity during larval growth. Using functional imaging and behavioral analysis we show that loss of Tao-induced ectopic synapses with inappropriate partner neurons are functional and alter behavioral responses in a connection-specific manner. Our data show that fine-tuning of synaptic growth by Tao kinase is required for maintaining specificity and behavioral output of the neuronal network during animal growth.
感觉回路通常在早期发育过程中建立，然而，在生物生长过程中，回路的特异性和功能是如何维持的，这一点尚未阐明。为了深入了解这一问题，我们在果蝇伤害感受网络的幼虫发育过程中，定量研究了突触生长和连接。我们表明，初级伤害感受器与其下游神经元之间的连接性与动物的大小成正比。我们进一步鉴定了保守的 Ste20 样激酶 Tao 作为突触生长的负调节因子，它是维持回路特异性和连接性所必需的。Tao 激酶的缺失会导致突触后特化过度和幼虫生长过程中连接异常。通过功能成像和行为分析，我们表明 Tao 诱导的与不适当的神经元伙伴形成的异位突触是功能性的，并以连接特异性的方式改变行为反应。我们的数据表明，Tao 激酶对突触生长的微调是维持神经元网络在动物生长过程中的特异性和行为输出所必需的。
