CONTROL OF EPITHELIAL SHEET MOVEMENT IN C ELEGANS
CONTROL OF EPITHELIAL SHEET MOVEMENT IN C ELEGANS
批准号:
6181295
负责人:
Jeffrey D Hardin
金额:
$18.38万
依托单位国家:
美国
项目类别:
财政年份:
1998
资助国家:
美国
项目状态:
已结题
起止时间:
1998-08-01 至 2002-07-31
关键词:
Caenorhabditis elegans affinity chromatography biological signal transduction cadherins cell migration epithelium gene complementation gene expression gene interaction gene mutation genetic mapping genetically modified animals green fluorescent proteins histogenesis in situ hybridization kinesin northern blottings phenotype polymerase chain reaction protein structure function single cell analysis stainings transfection
中文摘要
了解上皮层如何移动以及调节其移动的因素
对于理解许多影响人类健康的事件至关重要,
包括胎儿发育和转移生长的控制,
癌线虫C. elegans是一个
用于研究上皮形态发生的强大模型系统。我们有
进行了一个突变的筛选,影响皮下封闭,
具体的方法,我们建议分析我们克隆的基因,以获得一个
更好地理解特定的分子病变是如何识别的
蛋白质影响单细胞分辨率的上皮形态发生。这
建议有四个主要目标:
(1)确定连环蛋白/钙粘蛋白同源物在封闭过程中的作用。我们
将分析hmp-1(一种α-
连环蛋白)、hmp-2(一种β-连环蛋白)和hMR-1(一种钙粘蛋白)
突变体、嵌合体和生殖系嵌合体。我们还将测试
通过建立几个转基因系来研究hmp-2的形态发生作用
含有各种嵌合构建体,
与β-连环蛋白相关的功能。
(2)定义驱动蛋白样蛋白ZEN-4在封闭过程中的作用。
zen-4编码类似于脊椎动物CHO 1的驱动蛋白样蛋白
抗原的我们将分析zen-4纯合子的外壳缺陷。最后,
我们将测试ZEN-4蛋白是否以类似于
通过产生携带热休克构建体的转基因系,
以及通过使用培养的细胞进行转染实验。
(3)确定部分渗透突变vab-9在
附件。我们已经获得了vab-9的粘粒拯救,这表明了一致的
胚胎中的外壳缺陷和其他形态发生异常,
幼虫我们将缩小拯救区域,以确定编码基因
vab-9蛋白,通过产生试剂来表征其位置,
检查与其他VAB的基因相互作用。
(4)定义新突变在圈地过程中的作用。我们有
部分表征的额外突变,
渗透性外壳缺陷(合子、致死、外壳、缺陷或zen
突变体)以及显示不完全渗透封闭的突变
缺陷和其他形态发生过程中的缺陷(
上皮缺陷或MED)。作为长期目标,我们将继续
几个新zen和med位点的初步表征
作为这些研究的结果,我们希望能够更好地了解
已识别分子中的特定病变如何引起特定
上皮形态发生过程中的细胞缺陷。
英文摘要
Understand how epithelial sheets move and what regulates their movement is
fundamental for understanding many events impacting human health,
including fetal development and the control of metastatic growth in
cancer. The embryonic hypodermis of the nematode, C. elegans, is a
powerful model system for studying epithelial morphogenesis. We have
carried out a screen for mutations which affect hypodermal enclosure in
specific ways, and we propose to analyze genes we have cloned to gain a
greater understanding of how specific molecular lesions in identified
proteins affect epithelial morphogenesis at single-cell resolution. This
proposal has four major aims:
(1) Defining the role of catenin/cadherin homologues during enclosure. We
will analyze the specific defects in embryos mutant for hmp-1 (an alpha-
catenin), hmp-2 (a beta-catenin), and hmr-1 (a cadherin) in multiple
mutants, mosaics, and germline mosaics. We will also test the
morphogenetic role of hmp-2 by creating several transgenic lines
containing various chimeric constructs that cannot perform the signaling
functions associated with beta-catenins.
(2) Defining the role of the kinesin-like protein ZEN-4 during enclosure.
zen-4 encodes a kinesin-like protein similar to the vertebrate CHO1
antigen. We will analyze enclosure defects in zen-4 homozygotes. Finally,
we will test whether the ZEN-4 protein functions in a manner similar to
the CHO1 KRP by generating transgenic lines carrying heat-shock constructs
and by performing transfection experiments using cultured cells.
(3) Defining the role of the partially penetrant mutation vab-9 during
enclosure. We have obtained cosmid rescue of vab-9, which shows consistent
enclosure defects and other morphogenetic abnormalities in embryos and
larvae. We will narrow the rescuing region to identify the gene encoded by
vab-9 protein, by generating reagents to characterize its location, and by
examining genetic interactions with other vabs.
(4) Defining the role of novel mutations during enclosure. We have
partially characterized additional mutations that show completely
penetrant enclosure defects (zygotic, lethal, enclosure, defective, or zen
mutants) as well as mutations that show incompletely penetrant enclosure
defects, and defects in other morphogenetic processes (morphogenesis of
epithelial defective, or med). As a long-term goal, we will continue
initial characterization of several novel zen and med loci.
As a result of these studies, we expect to gain a greater understanding of
how specific lesions in identified molecules give rise to specific
cellular defects during epithelial morphogenesis.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Regulation of dynamic actin networks during epithelial morphogenesis
-
批准号:10617348
-
项目类别:
-
资助金额:$55.57万
-
财政年份:2022
-
负责人:Jeffrey D Hardin
-
依托单位:
Regulation of dynamic actin networks during epithelial morphogenesis
-
批准号:10797655
-
项目类别:
-
资助金额:$13.3万
-
财政年份:2022
-
负责人:Jeffrey D Hardin
-
依托单位:
Regulation of dynamic actin networks during epithelial morphogenesis
-
批准号:10406751
-
项目类别:
-
资助金额:$55.57万
-
财政年份:2022
-
负责人:Jeffrey D Hardin
-
依托单位:
Trio/CARMIL Regulation of Epithelial Cell Rearrangement
-
批准号:9903409
-
项目类别:
-
资助金额:$30.09万
-
财政年份:2018
-
负责人:Jeffrey D Hardin
-
依托单位:
Structure and regulation of beta-catenin during cell-cell adhesion
-
批准号:8320628
-
项目类别:
-
资助金额:$18.41万
-
财政年份:2012
-
负责人:Jeffrey D Hardin
-
依托单位:
Structure and regulation of beta-catenin during cell-cell adhesion
-
批准号:8431361
-
项目类别:
-
资助金额:$21.04万
-
财政年份:2012
-
负责人:Jeffrey D Hardin
-
依托单位:
Mechanisms of Junctional Actin Recruitment in C. elegans
-
批准号:7932347
-
项目类别:
-
资助金额:$5.02万
-
财政年份:2009
-
负责人:Jeffrey D Hardin
-
依托单位:
srGAP and the cadherin complex during morphogenesis in C. elegans
-
批准号:8506909
-
项目类别:
-
资助金额:$34.55万
-
财政年份:1998
-
负责人:Jeffrey D Hardin
-
依托单位:
Mechanisms of Junctional Actin Recruitment in C. elegans
-
批准号:7647211
-
项目类别:
-
资助金额:$33.8万
-
财政年份:1998
-
负责人:Jeffrey D Hardin
-
依托单位:
srGAP and the cadherin complex during morphogenesis in C. elegans
-
批准号:8880234
-
项目类别:
-
资助金额:$34.55万
-
财政年份:1998
-
负责人:Jeffrey D Hardin
-
依托单位:
CONTROL OF EPITHELIAL SHEET MOVEMENT IN C ELEGANS
-
批准号:6019472
-
项目类别:
-
资助金额:$17.84万
-
财政年份:1998
-
负责人:Jeffrey D Hardin
-
依托单位:
CONTROL OF EPITHELIAL SHEET MOVEMENT IN C ELEGANS
-
批准号:6386974
-
项目类别:
-
资助金额:$18.93万
-
财政年份:1998
-
负责人:Jeffrey D Hardin
-
依托单位:
Regulation of Epidermal Junctions in C. elegans
-
批准号:6785056
-
项目类别:
-
资助金额:$28.6万
-
财政年份:1998
-
负责人:Jeffrey D Hardin
-
依托单位:
CONTROL OF EPITHELIAL SHEET MOVEMENT IN C ELEGANS
-
批准号:2680752
-
项目类别:
-
资助金额:$18.47万
-
财政年份:1998
-
负责人:Jeffrey D Hardin
-
依托单位:
Regulation of Epidermal Junctions in C. elegans
-
批准号:7048593
-
项目类别:
-
资助金额:$35.0万
-
财政年份:1998
-
负责人:Jeffrey D Hardin
-
依托单位:
CONTROL OF EPITHELIAL SHEET MOVEMENT IN C ELEGANS
-
批准号:6696411
-
项目类别:
-
资助金额:$6.38万
-
财政年份:1998
-
负责人:Jeffrey D Hardin
-
依托单位:
srGAP and the cadherin complex during morphogenesis in C. elegans
-
批准号:9548360
-
项目类别:
-
资助金额:$11.7万
-
财政年份:1998
-
负责人:Jeffrey D Hardin
-
依托单位:
Mechanisms of Junctional Actin Recruitment in C. elegans
-
批准号:7808905
-
项目类别:
-
资助金额:$33.47万
-
财政年份:1998
-
负责人:Jeffrey D Hardin
-
依托单位:
Regulation of Epidermal Junctions in C. elegans
-
批准号:6921048
-
项目类别:
-
资助金额:$7.28万
-
财政年份:1998
-
负责人:Jeffrey D Hardin
-
依托单位:
Mechanisms of Junctional Actin Recruitment in C. elegans
-
批准号:8071562
-
项目类别:
-
资助金额:$33.13万
-
财政年份:1998
-
负责人:Jeffrey D Hardin
-
依托单位:
海外基金