Regulation of mediolateral cell polarity by PCP and notochord boundary signaling

PCP 和脊索边界信号传导调节内侧细胞极性

基本信息

批准号：
9055556
负责人：
Margot L.K. Williams
金额：
$ 5.61万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-06-01 至 2017-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9055556
关键词：
4D Imaging Alleles Animals Anterior Cell Polarity Cells Cessation of life Chromatin Complex Craniorachischises Cre-LoxP Cues Data Defect Deposition Development Embryo Embryonic Development Enhancers Exhibits Extracellular Matrix Failure Fetus Fishes Future Gastrula Gene Expression Genes Head Intercalated Cell Life Ligands Mediating Mesoderm Mesoderm Cell Modeling Molecular Molecular Profiling Morphogenesis Mutation Nature Neural Tube Closure Paraxial Mesoderm Pathway interactions Pattern Phenotype Population Process Regulation Reporting Role Signal Transduction Somites Spinal Dysraphism System Tail Testing Time Transgenic Organisms Transplantation Zebrafish base cell behavior cell motility cell type disability embryo tissue gastrulation intercalation mutant notochord novel overexpression planar cell polarity polarized cell public health relevance receptor response

项目摘要

DESCRIPTION (provided by applicant): All animal embryos, which begin as a disc or sphere, form an elongated body axis with a head on one end and a tail on the other. This fundamental process of axial elongation is accomplished by convergence and extension (C&E) of embryonic tissues, a process driven by polarized cell behaviors such as cell migration and mediolateral (ML) intercalation during gastrulation. Although molecular regulation of ML cell polarity in embryonic tissues is largely attributed to planar cell polarity (PCP) signaling, there is evidence that signals from the notochord-somite boundary (NSB) are also involved. The nature of this NSB signal and its relationship to PCP signaling are not understood. The Solnica-Krezel lab has identified the chromatin factor Ugly duckling (Udu)/Gon4l as a novel regulator of C&E in zebrafish. Maternal zygotic (MZ) udu mutant embryos display an extremely short anterior-posterior axis, and interestingly, abnormal NSB and reduced ML polarity of boundary-adjacent cells. Complete loss of udu/gon4l function enhances axis elongation defects in PCP mutant embryos, and PCP-dependent cell polarity appears to be unaffected in MZudu embryos, suggesting that udu/gon4l regulates ML cell polarity in parallel to the PCP pathway. We found that expression of slit3, which encodes a repulsive ECM ligand, is increased in MZudu embryos. Expression of Slit3 and its Robo receptors in the axial mesoderm of WT embryos predict a role for Slit-Robo signaling in formation of normal axial mesoderm and the NSB. Furthermore, overexpression of slit3 disrupts NSB formation and C&E in zebrafish embryos, and exacerbates axis elongation defects in PCP mutants. I hypothesize that udu/gon4l is required for intact Slit-Robo signaling at the NSB, which mediates a novel polarity cue that acts in parallel to PCP to regulate ML cell polarity underlying C&E. Characterization of this novel polarity cue, and its relationship to known polarity signals, will further our understanding of how complex positional and morphogenetic cues are coordinated during vertebrate embryogenesis.

描述（由申请人提供）：所有动物胚胎（从圆盘或球体开始）形成一个伸长的身体轴，头在一端，另一端为尾巴。轴向伸长的基本过程是通过胚胎组织的收敛和延伸（C＆E）来完成的，胚胎组织是由胃肠道造成的偏振细胞行为（例如细胞迁移和中外侧（ML）插入过程中）驱动的过程。尽管胚胎组织中ML细胞极性的分子调节主要归因于平面细胞极性（PCP）信号传导，但也有证据表明，来自脊索明石边界（NSB）的信号也涉及。该NSB信号的性质及其与PCP信号的关系尚不清楚。 Solnica-krezel Lab已将染色质因子丑陋的小鸭（UDU）/GON4L确定为斑马鱼中C＆E的新型调节剂。母体合子（MZ）UDU突变胚胎显示出极短的前后轴，有趣的是，NSB异常的NSB和降低了边界粘附细胞的ML极性。 UDU/GON4L功能的完全损失增强了PCP突变胚胎中的轴伸长缺陷，而PCP依赖性细胞极性似乎不受MZUDU胚胎的影响，这表明UDU/GON4L在与PCP途径平行的ML细胞极性调节ML细胞极性。我们发现编码排斥ECM配体的SLIT3的表达在Mzudu胚胎中增加。 slit3及其在WT胚胎轴向中胚层中的机器人受体的表达预测了裂隙 - 罗布信号传导在形成正常轴向中胚层和NSB中的作用。此外，SLIT3的过表达会破坏斑马鱼胚胎中的NSB形成和C＆E，并加剧PCP突变体中的轴伸长缺陷。我假设UDU/GON4L对于NSB的完整缝隙 - 摩布信号传导是必需的，NSB介导了一种与PCP并行作用以调节C＆E基础的ML细胞极性的新型极性提示。这种新颖的极性提示的表征及其与已知的极性信号的关系，将进一步了解我们对在脊椎动物胚胎发生过程中如何协调复杂的位置和形态发生线索的理解。