Systematic analysis of expression and function of developmental genes of model organisms towards computer simulation

模型生物发育基因表达和功能的计算机模拟系统分析

• 批准号: 12202003
• 负责人: KOHARA Yuji
• 金额: $ 245.38万
• 依托单位: National Institute of Genetics
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12202003/
• 关键词: Nematode; Cell lineage; EST; whole mount in situ Hybridization; RNAi; Clustering analysis; Computer simulation; Reaction-diffusion system; EST; whole mount in situ ハイブリダイゼーション; コンピュータシミュレーション; 4D顕微鏡; 発生; cDNA; alternative splicing; in situハ

1) We obtained 130,000 ESTs of the nematode C.elegans, from which we identified the gene structures of 14,000 unique cDNAs. We performed whole mount in situ hybridization with the unique cDNA set. All the information together with the description of RNAi phenotypes of 900 genes was stored and opened at our WWW-based database "NEXTDB" <http://nematode.lab.nig.ac.jp>. We have performed many collaborations based on the data in the database.2) We studied on the translational control mechanism of maternal mRNAs, finding the combinatorial regulation of the translation of glp-1 mRNA by gld-1, pos-1 and spn-4 gene products and the fine tuning by poly-A length.3) We performed EST/genome analysis of another nematode Diploscapter sp., which has a different cell cleavage and arrangement pattern until gastrulation stage. We are interested to compare gene expression and function between these different developmental systems. From 70,000 cDNA clones, 10,000 EST clusters were identified, of which 5,800 clusters had homologs to C.elegans. We also performed a low coverage (1X) whole-genome shotgun sequencing of this worm and found additional 1,000 homologs. All the results were also incorporated to NEXTDB.4) Cellular arrangements are important for cell-fate determination in development. We constructed a physical model for C.elegans embryo up to gastrulation stage (28 cell stage) using deformable and dividable polyhedrons. We further implemented microtubles and centrosomes, and we performed computer simulation analysis to get the parameters that reproduced the phenotype of wild type and mutant embryos.5) Based on the reaction-diffusion model, a mechanism for autonomous pattern formation in the animal skin has been elucidated.

1)我们获得了130，000条线虫的EST，从中我们鉴定了14，000个独特cDNA的基因结构。我们用这套独特的cDNA序列进行了全标本原位杂交。所有信息连同900个基因的RNAi表型描述一起存储在我们的基于WWW的数据库“NEXTDB”<http://nematode.lab.nig.ac.jp>中。2）研究了母体mRNA的翻译调控机制，发现glp-1 mRNA的翻译受gld-1、pos-1和spn-4基因产物的调控，以及poly-A长度的微调。3）对另一种线虫Diploscillussp.进行了EST/基因组分析，其具有不同的细胞分裂和排列模式直到原肠胚形成阶段。我们有兴趣比较这些不同发育系统之间的基因表达和功能。从70，000个cDNA克隆中，鉴定出10，000个EST簇，其中5，800个簇与秀丽隐杆线虫具有同源性。我们还对该蠕虫进行了低覆盖率（1X）全基因组鸟枪测序，并发现了另外1，000个同源物。所有结果也被并入NEXTDB。4）细胞排列对于发育中的细胞命运决定是重要的。我们利用可变形和可分割的多面体构建了线虫胚胎至原肠胚形成阶段（28细胞期）的物理模型。我们进一步实现了微管和中心体，并进行了计算机模拟分析，以获得再现野生型和突变型胚胎表型的参数。5）基于反应扩散模型，阐明了动物皮肤中自主图案形成的机制。

项目成果

Traveling stripes on the skin of a mutant mouse

• DOI: 10.1073/pnas.1731184100
• 发表时间: 2003-08-19
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Suzuki, N;Hirata, M;Kondo, S
• 通讯作者: Kondo, S

TLR-independent control of innate immunity in C.elegans by the human SARM homolog, TIR-1, a TIR-domain adaptor protein.

人类 SARM 同源物 TIR-1（一种 TIR 结构域接头蛋白）对秀丽隐杆线虫先天免疫的 TLR 独立控制。

• 发表时间: 2004
• 期刊: Nature Immunology 5
• 作者: Carole Couillault;Nathalie Pujol;Jerome Reboul;Laurence Sabatier;Jean-Francois Guichou;Yuji Kohara;Jonathan J. Ewbank
• 通讯作者: Jonathan J. Ewbank

The C.elegans unc-32 gene encodes alternative forms of the 100-kDa a subunit of Vacuolar-ATPases.

线虫 unc-32 基因编码 100 kDa 液泡 ATP 酶亚基的替代形式。

• 发表时间: 2001
• 期刊: J. Biol. Chem. Vol. 276,Issue 15
• 作者: Nathalie Pujol;Claire Bonnerot;Jonathan Ewbank;Yuji Kohara;Danielle Thierry-Mieg
• 通讯作者: Danielle Thierry-Mieg

Yohei Sasagawa: "Caenorhabditis elegans RBX1 is essential for meiosis, mitotic chromosomal condensation and segregation, and cytokinesis."Genes to Cells. 8. 857-872 (2003)

Yohei Sasakawa：“秀丽隐杆线虫 RBX1 对于减数分裂、有丝分裂染色体浓缩和分离以及胞质分裂至关重要。”基因到细胞。

Suzuki, N.: "Traveling stripes on the skin of a mutant mouse."Proc.Natl.Acad.Sci.USA.. 17. 9680-9685 (2003)

Suzuki, N.：“突变小鼠皮肤上的旅行条纹。”Proc.Natl.Acad.Sci.USA.. 17. 9680-9685 (2003)