多效生长因子通过JNK信号通路负调控Schlafen2基因表达

实验室前期研究发现,多效生长因子（pleiotrophin,PTN）基因稳定沉默的小鼠胚胎成纤维细胞中Schlafen2 (Slfn2)基因高表达.为了探讨Ptn沉默诱导Slfn2基因表达可能涉及的信号通路,应用Western印迹检测外源性PTN因子（终浓度50 ng/μl）对Ptn沉默细胞JNK磷酸化水平的影响;应用Northern 印迹分别检测JNK和p38通路特异性抑制剂对Ptn沉默细胞Slfn2基因转录水平的影响.结果发现,Ptn沉默细胞内JNK磷酸化水平高于对照细胞,外源性PTN处理后沉默细胞内JNK磷酸化水平下调;阻断JNK通路呈时间依赖性抑制Ptn沉默细胞中Slfn2基因转录,阻断p38通路对Ptn沉默细胞中Slfn2转录水平没有明显影响结果提示,Ptn可能通过抑制其下游JNK/MAPK通路来负调控Slfn2的表达.     

lncRNA CCAT2调控SIRT1蛋白表达激活Wnt/β-catenin通路影响非小细胞肺癌细胞增殖和转移

该文旨在分析长链非编码RNA(lncRNA) CCAT2通过调控SIRT1蛋白的表达激活Wnt/β-catenin信号通路进而影响非小细胞肺癌细胞增殖和转移的机制。采用qRT-PCR检测肺癌组织及肺癌细胞株中lncRNA CCAT2的表达。利用卡方检验分析lncRNA CCAT2表达与肺癌患者临床病理特征的关系。CCK-8实验、划痕实验及Transwell实验观察敲低lncRNA CCAT2表达对肺癌细胞增殖、迁移及浸润能力的影响。Western blot检测敲低lncRNA CCAT2表达对H1975细胞株中SIRT1蛋白及Wnt/β-catenin信号通路蛋白表达的影响;以及敲低或过表达SIRT1对Wnt/β-catenin信号通路蛋白表达的影响。利用RNA免疫共沉淀(RIP)及RNA pull-down实验验证lncRNA CCAT2与SIRT1之间的相互作用。该研究得出,癌组织及肺癌细胞株中lncRNA CCAT2表达显著较高(P0.05),敲低lncRNA CCAT2表达能够抑制H1975细胞的增殖、迁移及浸润。敲低lncRNA CCAT2表达后,H1975细胞株中SIRT1、β-catenin、Cyclin D1、myc蛋白的表达降低;敲低SIRT1后,细胞核β-catenin蛋白、Cyclin D1、myc蛋白的表达均降低。与非特异性抗体比较,SIRT1抗体呈明显的lncRNA CCAT2富集;lncRNA CCAT2的截短突变组细胞中SIRT1相对表达量明显低于lncRNA CCAT2组。lncRNA CCAT2通过调控SIRT1蛋白表达激活Wnt/β-catenin信号通路进而促进肺癌细胞增殖、迁移及浸润,有望成为新的肿瘤标志物。     

RAB26通过激活β-catenin信号促进鼻咽癌细胞增殖

该文探讨了RAB26对鼻咽癌细胞增殖的影响及其机制。采用实时荧光定量PCR和免疫组织化学实验检测鼻咽癌组织及正常鼻咽上皮组织RAB26 mRNA和蛋白表达水平,并将免疫组织化学方法检测的RAB26表达水平与患者临床病理特征进行统计分析。在鼻咽癌CNE-2细胞过表达RAB26、在HNE1细胞敲降RAB26,分别建立过表达以及敲降细胞系。利用CCK-8增殖实验、细胞克隆形成实验及EdU增殖实验检测过表达和敲降RAB26对鼻咽癌细胞增殖的影响; Western blot检测过表达和敲降RAB26的鼻咽癌细胞RAB26, Wnt/β-catenin信号中的β-catenin、cyclin D1、c-Myc、survivin的蛋白水平及MAPK/ERK信号中的p-p38 MAPK/p38 MAPK、p-ERK/ERK的蛋白水平。细胞克隆形成实验检测CNE-2过表达RAB26细胞经不同照射剂量(0 Gy、2 Gy、4 Gy、6 Gy及8 Gy)X射线照射后的细胞活力。结果显示, RAB26在鼻咽癌中高表达; RAB26在鼻咽癌中的表达水平与肿瘤类型(r=0.294, P<0.05)和转移/复...     

PC-1解除S6K对AKT信号通路的负反馈抑制

目的:通过建立过表达PC-1的前列腺癌LNCaP细胞系及敲低PC-1表达的C4-2细胞系,探究PC-1激活AKT信号通路的分子机制。方法:将PC-1基因及针对PC-1的siRNA序列,分别克隆至慢病毒表达载体pCDH-EF1-Myc-MCS-T2A-Puro及干扰载体pSIH1-H1-Puro,包装成慢病毒后分别感染前列腺癌LNCaP及C4-2细胞,通过Western印迹鉴定PC-1过表达及敲低效果,并检测PI3K/AKT/mTOR信号通路相关蛋白S6K、AKT的磷酸化水平。结果:PC-1过表达时,S6K磷酸化水平下降,而AKT的磷酸化水平上升。结论:PC-1可以通过抑制S6K激酶活性,解除其对AKT的负反馈抑制作用,从而激活AKT激酶的活性。     

日本三角涡虫体内Djcullin1基因和Djtinp1基因的相互作用研究

Cullin1蛋白是细胞周期进展的重要参与者,也是泛素连接酶E3的重要骨架蛋白。TGF-β信号通路在涡虫再生中发挥着重要作用,其下游分子TGF-β诱导核蛋白(Tinp1)也参与日本三角涡虫Dugesia japonica再生。虽然cullin1基因和tinp1基因在涡虫体内均呈阳性表达,但二者之间的关系还不清楚。本研究采用RNA干扰技术(RNAi)敲减日本三角涡虫体内Djcullin1基因的表达,然后运用整体原位杂交及Western Blotting技术检测基因敲减后TGF-β信号通路相关分子在涡虫体内的表达。结果显示,敲减日本三角涡虫Djcullin1基因可明显增强TGF-β信号通路相关分子Smad2/3及Smad4的表达,Tinp1的表达也明显增强。这些数据表明,在日本三角涡虫体内敲减Djcullin1基因可负性调控TGF-β信号通路和Djtinp1基因的表达。同时,敲减涡虫Djtinp1基因可增强Djcullin1基因及蛋白的表达,以上结果说明,这2个基因之间存在互相调节作用,Djtinp1基因反作用于Djcullin1基因的原因未知。     

Rspo1对雌性脊椎动物性别分化的功能

长期以来雌性脊椎动物的性别分化被认为是一个“默认”的程序.但是近些年研究发现,Rspo1基因的突变或缺失可导致哺乳动物XX型个体性反转为雄性.Rspo1在鱼类、两栖爬行类、鸟类和哺乳类动物性腺发育的不同阶段表达,其表达在雌雄个体性别分化时期有差异,是潜在的性别调控基因.Rspo1在性别发育早期可通过Wnt/β-catenin信号通路调控性腺分化相关因子的表达,影响原始生殖细胞分裂增殖、细胞周期和生长发育,参与调控性腺中体细胞的分化.本文总结了近年来Rspo1在脊椎动物中的表达调控及其在雌性性别决定方面功能的研究进展.     

Rspo1、LGR5、NF-κB/p65在胃癌中的表达及其临床意义

目的 通过检测特异性顶部盘状底板反应蛋白1(Rspo1)、富含亮氨酸的重复G蛋白偶联受体5(LGR5)与核转录因子κB/p65(NF-κB/p65)在人胃癌中的表达水平及与临床病理因素及预后之间的关系,并分析三者在胃癌发生发展中发挥的作用。方法 免疫组织化学SP法测定Rspo1、LGR5及NF-κB/p65在115例胃癌组织标本及20例正常组织标本中的表达。结果 Rspo1、LGR5、NF-κB/p65在胃癌中表达较正常组织增高;Rspo1、LGR5、NF-κB/p65的表达与浸润深度、TNM分期、淋巴结及远处转移有关,同时Rspo1表达与肿瘤大小、LGR5表达与肿瘤大小及分化程度有关;胃癌组织中Rspo1与LGR5、NF-κB/p65的表达呈正相关;Kaplan-Meier分析显示Rspo1、LGR5和NF-κB/p65表达阳性组3年生存率均低于阴性组;单因素Cox分析提示肿瘤大小、分化程度、浸润深度、淋巴结转移、远处转移、Rspo1、LGR5、NF-κB/p65阳性是影响胃癌患者预后的危险因素;多因素Cox分析提示淋巴结转移、远处转移、Rspo1及LGR5阳性是影响胃癌患者预后的独立危险因素。结论 Rspo1、LGR5、NF-κB/p65的表达与胃癌的发生发展有关;Rspo1-LGR5在激活Wnt/β-catenin通路的同时可能激活NF-κB通路,二者对胃癌发展有协同作用。     

S100A9对宫颈癌Hela细胞的增殖和迁移的影响及其机制探讨

为初步探讨S100A9在宫颈癌中的生物学作用,利用携带有人S100A9基因的腺病毒(Adh S100A9)感染于低表达S100A9的宫颈癌Hela细胞,通过MTT法检测细胞增殖能力,划痕愈合试验和Transwell试验检测细胞迁移能力,通过倒置显微镜观察细胞形态变化,采用RT-PCR和蛋白质印迹法检测上皮细胞标志蛋白E-钙黏着蛋白(E-cadherin,E-cad)、间质细胞标志蛋白波形蛋白(vimentin,Vim)及Wnt/β-联蛋白(β-catenin,β-cat)信号通路相关分子的表达。结果显示,与对照组相比,过表达S100A9的Hela细胞增殖活性增强、迁移率增高,细胞形态由"铺路石"样向"梭形"转变,排列紊乱,伴随E-cad降低(P0.05)和Vim升高(P0.01);同时,过表达S100A9的Hela细胞中Wnt/β-cat信号通路的关键分子β-联蛋白水平增加(P0.01),并且入核增多(P0.01),该通路的下游靶基因c-myc、Snail及Twist表达也明显上调。该研究结果提示,S100A9促进宫颈癌Hela细胞的增殖、迁移和上皮–间质转化(epithelial-mesenchymal transition,EMT),激活Wnt/β-cat信号通路;S100A9促进增殖和迁移作用的机制可能与其促进EMT和激活Wnt/β-cat信号通路相关。     

PCP通路调节平面细胞极性的建立

平面细胞极性(planar cell polarity,PCP)的建立是胚胎发育过程中的一个关键环节。PCP通路在进化上高度保守,包括"核心"PCP通路和"Ds/Ft"PCP通路,两者共同调节平面细胞极性的建立,导致细胞发生汇聚延伸(convergent extension,CE)运动和定向的细胞分裂(oriented cell division,OCD)。PCP通路的正确激活以及正常的细胞结构需要PCP蛋白的不对称性分布,由Wnt蛋白和Ft-Ds-Fj系统提供极性信号,激活下游效应器而产生。本文综述了PCP通路在平面细胞极性建立过程中的作用及分子机制,旨在为胚胎发育相关疾病积累理论基础。     

Pygo基因的细胞定位及其在果蝇发育过程中的表达(英文)

Wingless信号传导是果蝇胚胎和幼虫发育过程中的一个关键性的信号传导通路。已鉴定出来许多参与Wg Wnt信号传导的Wg或其脊椎动物同源基因Wnt下游传导通路的基因。Wg下游的Wg信号传导是由核TCF LEF 1通过Armadillo (Arm) β catenin介导的。pygopus (pygo)是一个最近发现的Wg Wnt信号传导通路新成员。通过细胞定位实验发现pygo专一性的表达在细胞核中。运用反义mRNA作探针的原位杂交技术 ,观察到了pygo基因在果蝇胚胎中的表达特性。虽然pygo普遍表达于果蝇胚胎发生全过程 ,但pygo在前囊胚层 (pre blastoderm)中的表达水平相对较高 ,这说明胚胎发生过程中来自母方的贡献较高。在幼虫组织 (包括翅成虫盘 ,眼成虫盘和腿成虫盘 )的发育过程中 ,pygo的表达水平总的来说比较低。然而 ,比较翅成虫盘 ,眼成虫盘和腿成虫盘的pygo表达水平 ,则在翅成虫盘和腿成虫盘pygo的表达水平相对较高。     

Fyn/Yes and non-canonical Wnt signalling converge on RhoA in vertebrate gastrulation cell movements

Convergent extension (CE) cell movements during gastrulation mediate extension of the anterior-posterior body axis of vertebrate embryos. Non-canonical Wnt5 and Wnt11 signalling is essential for normal CE movements in vertebrate gastrulation. Here, we show that morpholino (MO)-mediated double knock-down of the Fyn and Yes tyrosine kinases in zebrafish embryos impaired normal CE cell movements, resembling the silberblick and pipetail mutants, caused by mutations in wnt11 and wnt5, respectively. Co-injection of Fyn/Yes- and Wnt11- or Wnt5-MO was synergistic, but wnt11 or wnt5 RNA did not rescue the Fyn/Yes knockdown or vice versa. Remarkably, active RhoA rescued the Fyn/Yes knockdown as well as the Wnt11 knockdown, indicating that Fyn/Yes and Wnt11 signalling converged on RhoA. Our results show that Fyn and Yes act together with non-canonical Wnt signalling via RhoA in CE cell movements during gastrulation.     

Waif1/5T4 inhibits Wnt/β-catenin signaling and activates noncanonical Wnt pathways by modifying LRP6 subcellular localization

Wnt proteins can activate distinct signaling pathways, but little is known about the mechanisms regulating pathway selection. Here we show that the metastasis-associated transmembrane protein Wnt-activated inhibitory factor 1 (Waif1/5T4) interferes with Wnt/β-catenin signaling and concomitantly activates noncanonical Wnt pathways. Waif1 inhibits β-catenin signaling in zebrafish and Xenopus embryos as well as in mammalian cells, and zebrafish waif1a acts as a direct feedback inhibitor of wnt8-mediated mesoderm and neuroectoderm patterning during zebrafish gastrulation. Waif1a binds to the Wnt coreceptor LRP6 and inhibits Wnt-induced LRP6 internalization into endocytic vesicles, a process that is required for pathway activation. Thus, Waif1a modifies Wnt/β-catenin signaling by regulating LRP6 subcellular localization. In addition, Waif1a enhances β-catenin-independent Wnt signaling in zebrafish embryos and Xenopus explants by promoting a noncanonical function of Dickkopf1. These results suggest that Waif1 modulates pathway selection in Wnt-receiving cells.     

Role of lbx2 in the noncanonical Wnt signaling pathway for convergence and extension movements and hypaxial myogenesis in zebrafish

It has been suggested that mouse lbx1 is essential for directing hypaxial myogenic precursor cell migration. In zebrafish, the expression of lbx1a, lbx1b, and lbx2 has been observed in pectoral fin buds. It has also been shown that knocking down endogenous lbx2 in zebrafish embryos diminishes myoD expression in the pectoral fin bud. However, downstream lbxs signals remain largely unexplored. Here, we describe a previously unknown function of zebrafish lbx2 (lbx2) during convergent extension (CE) movements. The abrogation of the lbx2 function by two non-overlapping morpholino oligonucleotides (MOs) resulted in the defective convergence and extension movements in morphants during gastrulation. Our transplantation studies further demonstrated that the overexpression of lbx2 autonomously promotes CE movements. Expression of wnt5b is significantly reduced in lbx2 morphants. We have demonstrated that application of the wnt5b MO, a dominant-negative form of disheveled (Dvl) and a chemical inhibitor of Rho-associated kinase Y27632 in zebrafish embryos have effects reminiscent that are of the CE and hypaxial myogenesis defects observed in lbx2 morphants. Moreover, the CE and hypaxial mesoderm defects seen in lbx2 morphants can be rescued by co-injection with wnt5b or RhoA mRNA. However, this reduced level of active RhoA and hypaxial myogenesis defects in the embryos injected with the dominant-negative form of Dvl mRNA cannot be effectively restored by co-injection with lbx2 mRNA. Our results suggest that the key noncanonical Wnt signaling components Wnt5, Dvl, and RhoA are downstream effectors involved in the regulative roles of lbx2 in CE movement and hypaxial myogenesis during zebrafish embryogenesis.     

Wnt/PCP signaling controls intracellular position of MTOCs during gastrulation convergence and extension movements

During vertebrate gastrulation, convergence and extension cell movements are coordinated with the anteroposterior and mediolateral embryonic axes. Wnt planar cell polarity (Wnt/PCP) signaling polarizes the motile behaviors of cells with respect to the anteroposterior embryonic axis. Understanding how Wnt/PCP signaling mediates convergence and extension (C&E) movements requires analysis of the mechanisms employed to alter cell morphology and behavior with respect to embryonic polarity. Here, we examine the interactions between the microtubule cytoskeleton and Wnt/PCP signaling during zebrafish gastrulation. First, we assessed the location of the centrosome/microtubule organizing center (MTOC) relative to the cell nucleus and the body axes, as a marker of cell polarity. The intracellular position of MTOCs was polarized, perpendicular to the plane of the germ layers, independently of Wnt/PCP signaling. In addition, this position became biased posteriorly and medially within the plane of the germ layers at the transition from mid- to late gastrulation and from slow to fast C&E movements. This depends on intact Wnt/PCP signaling through Knypek (Glypican4/6) and Dishevelled components. Second, we tested whether microtubules are required for planar cell polarization. Once the planar cell polarity is established, microtubules are not required for accumulation of Prickle at the anterior cell edge. However, microtubules are needed for cell-cell contacts and initiation of its anterior localization. Reciprocal interactions occur between Wnt/PCP signaling and microtubule cytoskeleton during C&E gastrulation movements. Wnt/PCP signaling influences the polarity of the microtubule cytoskeleton and, conversely, microtubules are required for the asymmetric distribution of Wnt/PCP pathway components.     

Rspo1/Wnt signaling promotes angiogenesis via Vegfc/Vegfr3

Here, we show that a novel Rspo1-Wnt-Vegfc-Vegfr3 signaling pathway plays an essential role in developmental angiogenesis. A mutation in R-spondin1 (rspo1), a Wnt signaling regulator, was uncovered during a forward-genetic screen for angiogenesis-deficient mutants in the zebrafish. Embryos lacking rspo1 or the proposed rspo1 receptor kremen form primary vessels by vasculogenesis, but are defective in subsequent angiogenesis. Endothelial cell-autonomous inhibition of canonical Wnt signaling also blocks angiogenesis in vivo. The pro-angiogenic effects of Rspo1/Wnt signaling are mediated by Vegfc/Vegfr3(Flt4) signaling. Vegfc expression is dependent on Rspo1 and Wnt, and Vegfc and Vegfr3 are necessary to promote angiogenesis downstream from Rspo1-Wnt. As all of these molecules are expressed by the endothelium during sprouting stages, these results suggest that Rspo1-Wnt-VegfC-Vegfr3 signaling plays a crucial role as an endothelial-autonomous permissive cue for developmental angiogenesis.     

Prickle 1 regulates cell movements during gastrulation and neuronal migration in zebrafish

During vertebrate gastrulation, mesodermal and ectodermal cells undergo convergent extension, a process characterised by prominent cellular rearrangements in which polarised cells intercalate along the medio-lateral axis leading to elongation of the antero-posterior axis. Recently, it has become evident that a noncanonical Wnt/Frizzled (Fz)/Dishevelled (Dsh) signalling pathway, which is related to the planar-cell-polarity (PCP) pathway in flies, regulates convergent extension during vertebrate gastrulation. Here we isolate and functionally characterise a zebrafish homologue of Drosophila prickle (pk), a gene that is implicated in the regulation of PCP. Zebrafish pk1 is expressed maternally and in moving mesodermal precursors. Abrogation of Pk1 function by morpholino oligonucleotides leads to defective convergent extension movements, enhances the silberblick (slb)/wnt11 and pipetail (Ppt)/wnt5 phenotypes and suppresses the ability of Wnt11 to rescue the slb phenotype. Gain-of-function of Pk1 also inhibits convergent extension movements and enhances the slb phenotype, most likely caused by the ability of Pk1 to block the Fz7-dependent membrane localisation of Dsh by downregulating levels of Dsh protein. Furthermore, we show that pk1 interacts genetically with trilobite (tri)/strabismus to mediate the caudally directed migration of cranial motor neurons and convergent extension. These results indicate that, during zebrafish gastrulation Pk1 acts, in part, through interaction with the noncanonical Wnt11/Wnt5 pathway to regulate convergent extension cell movements, but is unlikely to simply be a linear component of this pathway. In addition, Pk1 interacts with Tri to mediate posterior migration of branchiomotor neurons, probably independent of the noncanonical Wnt pathway.     

Zebrafish Rho kinase 2 acts downstream of Wnt11 to mediate cell polarity and effective convergence and extension movements

BACKGROUND: During vertebrate gastrulation convergence and extension (CE), movements narrow and lengthen embryonic tissues. In Xenopus and zebrafish, a noncanonical Wnt signaling pathway constitutes the vertebrate counterpart to the Drosophila planar cell polarity pathway and regulates mediolateral cell polarization underlying CE. Despite the identification of several signaling molecules required for normal CE, the downstream transducers regulating individual cell behaviors driving CE are only beginning to be elucidated. Moreover, how defective mediolateral cell polarity impacts CE is not understood.RESULTS: Here, we show that overexpression of zebrafish dominant-negative Rho kinase 2 (dnRok2) disrupts CE without altering cell fates, phenocopying noncanonical Wnt signaling mutants. Moreover, Rho kinase 2 (Rok2) overexpression partially suppresses the slb/wnt11 gastrulation phenotype, and ectopic expression of noncanonical Wnts modulates Rok2 intracellular distribution. In addition, time-lapse analyses associate defective dorsal convergence movements with impaired cell elongation, mediolateral orientation, and consequently failure to migrate along straight paths. Transplantation experiments reveal that dnRok2 cells in wild-type hosts neither elongate nor orient their axes. In contrast, wild-type cells are able to elongate their cell bodies in dnRok2 hosts, even though they fail to orient their axes.CONCLUSIONS: During zebrafish gastrulation, Rok2 acts downstream of noncanonical Wnt11 signaling to mediate mediolateral cell elongation required for dorsal cell movement along straight paths. Furthermore, elongation and orientation of the cell body are independent properties that require both cell-autonomous and nonautonomous Rok2 function.     

RhoA acts downstream of Wnt5 and Wnt11 to regulate convergence and extension movements by involving effectors Rho kinase and Diaphanous: use of zebrafish as an in vivo model for GTPase signaling

Gastrulation shapes the early embryos by forming three germ layers, ectoderm, mesoderm and endoderm. In vertebrates, this process requires massive cell rearrangement including convergence and extension (CE) movements that involve narrowing and lengthening of embryonic tissues as well as cell elongation. Such polarization and movements require precise reorganization and regulation of the cytoskeleton network and cell adhesion. Rho small GTPases are key regulators for dynamic actin cytoskeleton. However, the signaling mechanisms underlying their functions in CE remain to be further elucidated. We have cloned the zebrafish Danio rerio rhoA and by capitalizing on the specific functional knockdown using morpholinos against rhoA and the availability of CE mutants defective in Wnt signaling, we showed that rhoA morphants were reminiscent to noncanonical wnt mutants with serious disruption in CE movements. Injection of rhoA mRNA effectively rescued such defects in wnt5 and wnt11 mutants. Furthermore, CE defects in rhoA knockdown or wnt mutants can be suppressed through functional bypass after ectopic expression of the two mammalian Rho effectors, the Rho kinase and Diaphanous (mDia). These results provide the first evidence that the RhoA in vivo acts downstream of Wnt5 and Wnt11 to effect, without affecting cell fates, on the CE movements in zebrafish embryos. Significantly, it elicits such effect via both effectors, Rho kinase and Dia. These findings also support the versatility of the zebrafish as a model to further investigate the roles of various classes of small GTPases in regulating cell dynamics in vivo.     

Zebrafish colgate/hdac1 functions in the non-canonical Wnt pathway during axial extension and in Wnt-independent branchiomotor neuron migration

Vertebrate gastrulation involves the coordinated movements of populations of cells. These movements include cellular rearrangements in which cells polarize along their medio-lateral axes leading to cell intercalations that result in elongation of the body axis. Molecular analysis of this process has implicated the non-canonical Wnt/Frizzled signaling pathway that is similar to the planar cell polarity pathway (PCP) in Drosophila. Here we describe a zebrafish mutant, colgate (col), which displays defects in the extension of the body axis and the migration of branchiomotor neurons. Activation of the non-canonical Wnt/PCP pathway in these mutant embryos by overexpressing DeltaNdishevelled, rho kinase2 and van gogh-like protein 2 (vangl2) rescues the extension defects suggesting that col acts as a positive regulator of the non-canonical Wnt/PCP pathway. Further, we show that col normally regulates the caudal migration of nVII facial hindbrain branchiomotor neurons and that the mutant phenotype can be rescued by misexpression of vangl2 independent of the Wnt/PCP pathway. We cloned the col locus and found that it encodes histone deacetylase1 (hdac1). Our previous results and studies by others have implicated hdac1 in repressing the canonical Wnt pathway. Here, we demonstrate novel roles for zebrafish hdac1 in activating non-canonical Wnt/PCP signaling underlying axial extension and in promoting Wnt-independent caudal migration of a subset of hindbrain branchiomotor neurons.