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Gut–neuron interaction via Hh signaling regulates intestinal progenitor cell differentiation in Drosophila

机译:Hh信号通过肠道-神经元相互作用调节果蝇的肠道祖细胞分化

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Intestinal homeostasis is maintained by intestinal stem cells (ISCs) and their progenies. A complex autonomic nervous system spreads over posterior intestine. However, whether and how neurons regulate posterior intestinal homeostasis is largely unknown. Here we report that neurons regulate Drosophila posterior intestinal homeostasis. Specifically, downregulation of neuronal Hedgehog (Hh) signaling inhibits the differentiation of ISCs toward enterocytes (ECs), whereas upregulated neuronal Hh signaling promotes such process. We demonstrate that, among multiple sources of Hh ligand, those secreted by ECs induces similar phenotypes as does neuronal Hh. In addition, intestinal JAK/STAT signaling responds to activated neuronal Hh signaling, suggesting that JAK/STAT signaling acts downstream of neuronal Hh signaling in intestine. Collectively, our results indicate that neuronal Hh signaling is essential for the determination of ISC fate.
机译:肠内稳态由肠干细胞(ISC)及其子代维持。复杂的自主神经系统遍布后肠。然而,神经元是否以及如何调节后肠稳态仍是未知的。在这里,我们报告神经元调节果蝇后肠稳态。具体而言,神经元刺猬(Hh)信号的下调抑制了ISC向肠上皮细胞(EC)的分化,而神经元Hh信号上调则促进了这种过程。我们证明,在Hh配体的多种来源中,EC分泌的那些与神经元Hh一样诱导相似的表型。另外,肠道JAK / STAT信号对激活的神经元Hh信号有反应,表明JAK / STAT信号在肠道神经元Hh信号的下游起作用。总的来说,我们的结果表明神经元Hh信号对于确定ISC命运至关重要。

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