Caenorhabditis elegans larval development requires the function of the two Canal-Associated Neurons (CANs): killing the CANs by laser microsurgery or disrupting their development by mutating the gene ceh-10 results in early larval arrest. How these cells promote larval development, however, remains a mystery. In screens for mutations that bypass CAN function, we identified the gene kin-29, which encodes a member of the Salt-Inducible Kinase (SIK) family and a component of a conserved pathway that regulates various C. elegans phenotypes. Like kin-29 loss, gain-of-function mutations in genes that may act upstream of kin-29 or growth in cyclic-AMP analogs bypassed ceh-10 larval arrest, suggesting that a conserved adenylyl cyclase/PKA pathway inhibits KIN-29 to promote larval development, and that loss of CAN function results in dysregulation of KIN-29 and larval arrest. The adenylyl cyclase ACY-2 mediates CAN-dependent larval development: acy-2 mutant larvae arrested development with a similar phenotype to ceh-10 mutants, and the arrest phenotype was suppressed by mutations in kin-29 ACY-2 is expressed predominantly in the CANs, and we provide evidence that the acy-2 functions in the CANs to promote larval development. By contrast, cell-specific expression experiments suggest that kin-29 acts in both the hypodermis and neurons, but not in the CANs. Based on our findings, we propose two models for how ACY-2 activity in the CANs regulates KIN-29 in target cells.

中文翻译：

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神秘的运河相关神经元通过 cAMP 信号通路调节秀丽隐杆线虫幼虫的发育。

秀丽隐杆线虫幼虫的发育需要两个运河相关神经元 (CAN) 的功能：通过激光显微手术杀死 CAN，或通过突变基因ceh-10来破坏其发育，从而导致早期幼虫停滞。然而，这些细胞如何促进幼虫发育仍然是个谜。在筛选绕过 CAN 功能的突变时，我们鉴定了基因kin-29，该基因编码盐诱导激酶 (SIK) 家族的成员，也是调节各种线虫表型的保守途径的组成部分。与kin-29丢失一样，可能作用于kin-29上游的基因的功能获得性突变或环化 AMP 类似物的生长绕过了ceh-10幼虫停滞，表明保守的腺苷酸环化酶/PKA 途径抑制 KIN-29促进幼虫发育，CAN 功能丧失会导致 KIN-29 失调和幼虫停滞。腺苷酸环化酶 ACY-2 介导 CAN 依赖性幼虫发育：acy-2突变体幼虫发育停滞，其表型与ceh-10突变体相似，并且停滞表型被kin-29突变抑制。ACY-2 主要在CAN 中，我们提供的证据表明acy-2在 CAN 中发挥促进幼虫发育的作用。相比之下，细胞特异性表达实验表明kin-29在皮下组织和神经元中起作用，但在CAN中不起作用。根据我们的发现，我们提出了两种模型来解释 CAN 中的 ACY-2 活性如何调节靶细胞中的 KIN-29。