Intraflagellar transport/Hedgehog-related signaling components couple sensory cilium morphology and serotonin biosynthesis in Caenorhabditis elegans.
Intraflagellar transport/Hedgehog-related signaling components couple sensory cilium morphology and serotonin biosynthesis in Caenorhabditis elegans.
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DOI：
10.1523/jneurosci.0044-09.2009
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发表时间：
2009-04-01
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影响因子：
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通讯作者：
Sze JY
中科院分区：
文献类型：
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作者：
Moussaif M;Sze JY
纤毛的鞭毛内转运被认为是脊椎动物和无脊椎动物胚胎模式形成过程中Hedgehog信号转导的重要媒介。在这里，我们发现Hh受体补丁相关因子DAF-6和鞭毛内转运通过重塑一对ADF - 5 -羟色胺能化学感觉神经元的树突纤毛结构来调节秀丽隐杆线虫动物血清素的产生。野生型动物在恶劣环境下，化学感觉神经元纤毛周围胶质样细胞中DAF-6的表达显著降低，导致纤毛结构重塑，ADF神经元中色氨酸羟化酶tph-1表达上调。当环境改善时，这些细胞和分子的修饰会被逆转。daf-6或鞭毛内转运的突变体组成性上调tph-1的表达。上位分析表明，DAF-6/纤束内转运和OCR-2/OSM-9 TRPV通道协同作用，调节ADF神经元中tph-1的两层激活。TRPV信号在有利条件和不利条件下都能激活tph-1的表达，而DAF-6在逆境下失活会导致tph-1的进一步上调，而不依赖于OCR-2/OSM-9的活性。行为分析表明，当环境改善时，血清素有助于幼体动物恢复发育。本研究揭示了5 -羟色胺能神经元的纤毛结构是调节5 -羟色胺产生的触发因素，并证明了一种与刺猬相关的信号成分受环境的动态调节，强调了秀丽线虫在应激和应激恢复下5 -羟色胺能神经元的神经可塑性。
Intraflagellar transport in cilia has been proposed as a crucial mediator of Hedgehog signal transduction during embryonic pattern formation in both vertebrates and invertebrates. Here, we show that the Hh receptor Patched-related factor DAF-6 and intraflagellar transport modulate serotonin production in Caenorhabditis elegans animals, by remodeling the architecture of dendritic cilia of a pair of ADF serotonergic chemosensory neurons. Wild-type animals under aversive environment drastically reduce DAF-6 expression in glia-like cells surrounding the cilia of chemosensory neurons, resulting in cilium structural remodeling and upregulation of the serotonin-biosynthesis enzyme tryptophan hydroxylase tph-1 in the ADF neurons. These cellular and molecular modifications are reversed when the environment improves. Mutants of daf-6 or intraflagellar transport constitutively upregulate tph-1 expression. Epistasis analyses indicate that DAF-6/intraflagellar transport and the OCR-2/OSM-9 TRPV channel act in concert, regulating two layers of activation of tph-1 in the ADF neurons. The TRPV signaling turns on tph-1 expression under favorable and aversive conditions, whereas inactivation of DAF-6 by stress results in further upregulation of tph-1 independently of OCR-2/OSM-9 activity. Behavioral analyses suggest that serotonin facilitates larval animals resuming development when the environment improves. Our study revealed the cilium structure of serotonergic neurons as a trigger of regulated serotonin production, and demonstrated that a Hedgehog-related signaling component is dynamically regulated by environment and underscores neuroplasticity of serotonergic neurons in C. elegans under stress and stress recovery.