Dcc regulates asymmetric outgrowth of forebrain neurons in zebrafish.
Dcc regulates asymmetric outgrowth of forebrain neurons in zebrafish.
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Dcc 调节斑马鱼前脑神经元的不对称生长
DOI：
10.1371/journal.pone.0036516
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Peng G
中科院分区：
文献类型：
--
作者：
Gao J;Zhang C;Yang B;Sun L;Zhang C;Westerfield M;Peng G
导向受体DCC(在结直肠癌中缺失)同源基因UNC-40调节秀丽线虫神经元的不对称发育，但目前尚不清楚DCC是否在脊椎动物神经元极性的指定中起作用。为了研究DCC在脊椎动物神经元不对称调节中的作用，我们研究了斑马鱼的前背侧端脑(ADT)神经元轴突。我们培育了在ADT神经元中表达光可转换荧光蛋白Kaeed的转基因斑马鱼动物，然后将Kaeed光转化为特异性标记ADT神经元轴突的基因。我们发现ADT轴突通常投射到腹侧。注射反义吗啉寡核苷酸使DCC功能下降，导致ADT神经元向背侧投射轴突。为了研究单个ADT神经元的轴突投射模式，我们使用前脑特异的启动子来标记单个ADT神经元来驱动荧光蛋白的表达。我们发现，在吗啡抑制DCC功能后，单个ADT神经元向背侧投射轴突或形成多个突起。我们进一步发现，DCC配体Netrin1的敲除也导致ADT神经元向背侧投射轴突。敲除与DCC密切相关的导向受体Negenin1可促进注射DCC吗啉的胚胎中异常背侧轴突的形成。这些实验首次提供了DCC调节脊椎动物前脑神经元极化轴突起始和不对称突起的证据。
The guidance receptor DCC (deleted in colorectal cancer) ortholog UNC-40 regulates neuronal asymmetry development in Caenorhabditis elegans, but it is not known whether DCC plays a role in the specification of neuronal polarity in vertebrates. To examine the roles of DCC in neuronal asymmetry regulation in vertebrates, we studied zebrafish anterior dorsal telencephalon (ADt) neuronal axons. We generated transgenic zebrafish animals expressing the photo-convertible fluorescent protein Kaede in ADt neurons and then photo-converted Kaede to label specifically the ADt neuron axons. We found that ADt axons normally project ventrally. Knock down of Dcc function by injecting antisense morpholino oligonucleotides caused the ADt neurons to project axons dorsally. To examine the axon projection pattern of individual ADt neurons, we labeled single ADt neurons using a forebrain-specific promoter to drive fluorescent protein expression. We found that individual ADt neurons projected axons dorsally or formed multiple processes after morpholino knock down of Dcc function. We further found that knock down of the Dcc ligand, Netrin1, also caused ADt neurons to project axons dorsally. Knockdown of Neogenin1, a guidance receptor closely related to Dcc, enhanced the formation of aberrant dorsal axons in embryos injected with Dcc morpholino. These experiments provide the first evidence that Dcc regulates polarized axon initiation and asymmetric outgrowth of forebrain neurons in vertebrates.
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影响因子：
1.5
作者：
DeLaurier, April;Eames, B. Frank;Blanco-Sanchez, Bernardo;Peng, Gang;He, Xinjun;Swartz, Mary E.;Ullmann, Bonnie;Westerfield, Monte;Kimmel, Charles B.
通讯作者：
Kimmel, Charles B.
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13.9
作者：
Barnes AP;Polleux F
通讯作者：
Polleux F
影响因子：
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作者：
Fricke, C;Chien, CB
通讯作者：
Chien, CB