Receptor tyrosine phosphatases guide vertebrate motor axons during development
Receptor tyrosine phosphatases guide vertebrate motor axons during development
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DOI：
10.1523/jneurosci.4531-04.2005
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发表时间：
2005-04-13
影响因子：
5.3
通讯作者：
Bixby, JL
中科院分区：
文献类型：
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作者：
Stepanek, L;Stoker, AW;Bixby, JL
果蝇神经系统发育过程中轴突的适当生长需要受体型蛋白酪氨酸磷酸酶（RPTP）。在脊椎动物中，IIa 型 RPTP [蛋白酪氨酸磷酸酶 (PTP)-delta、PTP-sigma 和 LAR（白细胞共同抗原相关）] 和 III 型 RPTP、O 型 PTP 受体 (TPRO) 与轴突生长的调节有关，但它们在发育轴突引导中的作用尚不清楚。 PTPRO、PTP-delta 和 PTP-sigma 在轴突发生期间分别在雏鸡运动神经元中表达。为了研究 RPTP 在体内轴突生长和引导中的潜在作用，我们使用双链 RNA (dsRNA) 干扰结合卵内电穿孔来降低胚胎鸡腰脊髓中 RPTP 的表达水平。尽管发育中的肢体神经的大多数分支看起来完全正常，但被确定为髂前肌的背神经明显受到 RPTP 的 dsRNA 敲除的影响。在用靶向 PTP-delta、PTP-sigma 或 PTPRO 的 dsRNA 处理的实验胚胎中，该神经表现出异常的束动、尺寸减小或完全缺失；对 PTPRO 的干扰产生了最严重的表型。用媒介物或用靶向胆碱乙酰转移酶或axonin-1的dsRNA电穿孔的对照胚胎没有表现出这种表型。令人惊讶的是，用靶向 PTP-delta 的 dsRNA 与 PTPRO 一起电穿孔的胚胎，或所有三种 RPTP 组合，与单独用 PTPRO 处理的胚胎相比，具有不太严重的表型。这一结果表明，IIa 型和 III 型 RPTP 之间的竞争可以调节运动轴突的生长，与果蝇中的发现一致。我们的结果表明，RPTP，尤其是 PTPRO，是轴突生长和发育中脊椎动物肢体的引导所必需的。
Receptor-type protein tyrosine phosphatases (RPTPs) are required for appropriate growth of axons during nervous system development in Drosophila. In the vertebrate, type IIa RPTPs [protein tyrosine phosphatase (PTP)-delta, PTP-sigma, and LAR (leukocyte common-antigen-related)] and the type III RPTP, PTP receptor type O ( TPRO), have been implicated in the regulation of axon growth, but their roles in developmental axon guidance are unclear. PTPRO, PTP-delta, and PTP-sigma are each expressed in chick motor neurons during the period of axonogenesis. To examine potential roles of RPTPs in axon growth and guidance in vivo, we used double- stranded RNA (dsRNA) interference combined with in ovo electroporation to knock down RPTP expression levels in the embryonic chick lumbar spinal cord. Although most branches of the developing limb nerves appeared grossly normal, a dorsal nerve identified as the anterior iliotibialis was clearly affected by dsRNA knock-down of RPTPs. In experimental embryos treated with dsRNA targeting PTP-delta, PTP-sigma, or PTPRO, this nerve showed abnormal fasciculation, was reduced in size, or was missing entirely; interference with PTPRO produced the most severe phenotypes. Control embryos electroporated with vehicle, or with dsRNA targeting choline acetyltransferase or axonin-1, did not exhibit this phenotype. Surprisingly, embryos electroporated with dsRNA targeting PTP-delta together with PTPRO, or all three RPTPs combined, had less severe phenotypes than embryos treated with PTPRO alone. This result suggests that competition between type IIa and type III RPTPs can regulate motor axon outgrowth, consistent with findings in Drosophila. Our results indicate that RPTPs, and especially PTPRO, are required for axon growth and guidance in the developing vertebrate limb.