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首页> 外文期刊>Cellular and molecular life sciences: CMLS >Protein tyrosine phosphatase receptor type O (Ptpro) regulates cerebellar formation during zebrafish development through modulating Fgf signaling
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Protein tyrosine phosphatase receptor type O (Ptpro) regulates cerebellar formation during zebrafish development through modulating Fgf signaling

机译：O型蛋白酪氨酸磷酸酶受体（Ptpro）通过调节Fgf信号传导调节斑马鱼发育过程中的小脑形成

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Protein activities controlled by receptor protein tyrosine phosphatases (RPTPs) play comparably important roles in transducing cell surface signals into the cytoplasm by protein tyrosine kinases. Previous studies showed that several RPTPs are involved in neuronal generation, migration, and axon guidance in Drosophila, and the vertebrate hippocampus, retina, and developing limbs. However, whether the protein tyrosine phosphatase type O (ptpro), one kind of RPTP, participates in regulating vertebrate brain development is largely unknown. We isolated the zebrafish ptpro gene and found that its transcripts are primarily expressed in the embryonic and adult central nervous system. Depletion of zebrafish embryonic Ptpro by antisense morpholino oligonucleotide knockdown resulted in prominent defects in the forebrain and cerebellum, and the injected larvae died on the 4th day post-fertilization (dpf). We further investigated the function of ptpro in cerebellar development and found that the expression of ephrin-A5b (efnA5b), a Fgf signaling induced cerebellum patterning factor, was decreased while the expression of dusp6, a negative-feedback gene of Fgf signaling in the midbrain-hindbrain boundary region, was notably induced in ptpro morphants. Further analyses demonstrated that cerebellar defects of ptpro morphants were partially rescued by inhibiting Fgf signaling. Moreover, Ptpro physically interacted with the Fgf receptor 1a (Fgfr1a) and dephosphorylated Fgfr1a in a dose-dependant manner. Therefore, our findings demonstrate that Ptpro activity is required for patterning the zebrafish embryonic brain. Specifically, Ptpro regulates cerebellar formation during zebrafish development through modulating Fgf signaling.
机译：受体蛋白酪氨酸磷酸酶（RPTP）控制的蛋白活性在通过蛋白酪氨酸激酶将细胞表面信号转导到细胞质中起着相当重要的作用。先前的研究表明，几种RPTP参与果蝇，脊椎动物海马，视网膜和发育中的肢体的神经元生成，迁移和轴突导向。但是，蛋白酪氨酸磷酸酶O型（ptpro）（一种RPTP）是否参与调节脊椎动物的大脑发育尚不清楚。我们分离了斑马鱼ptpro基因，发现其转录本主要在胚胎和成年中枢神经系统中表达。反义吗啉代寡核苷酸敲除耗尽了斑马鱼的胚胎Ptpro，导致了前脑和小脑的明显缺陷，并且注射的幼虫在受精后第4天死亡（dpf）。我们进一步研究了ptpro在小脑发育中的功能，发现ephrin-A5b（efnA5b）（一种Fgf信号诱导的小脑模式因子）的表达降低，而dusp6（Fgf信号的负反馈基因）在中脑的表达降低了。 hinprobrain边界区域，在ptpro morphant中显着诱导。进一步的分析表明，通过抑制Fgf信号传导可以部分挽救ptpro morphant的小脑缺陷。此外，Ptpro与Fgf受体1a（Fgfr1a）和脱磷酸的Fgfr1a发生剂量依赖性的物理相互作用。因此，我们的发现证明Ptpro活性是斑马鱼胚胎大脑构图所必需的。具体而言，Ptpro通过调节Fgf信号传导调节斑马鱼发育过程中的小脑形成。

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