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The morphogenetic contributions of SPARC and collagen IV during drosophila embryogenesis

SPARC 和 IV 型胶原在果蝇胚胎发生过程中的形态发生贡献

基本信息

批准号：
36708-2010
负责人：
Ringuette, Maurice
金额：
$ 1.97万
依托单位：
University of Toronto
依托单位国家：
加拿大
项目类别：
Discovery Grants Program - Individual
财政年份：
2014
资助国家：
加拿大
起止时间：
2014-01-01 至 2015-12-31
项目状态：
已结题

来源：
https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=544757
关键词：
morphogenetic contributions SPARC collagen IV

项目摘要

Shortly after fertilization, multicellular organisms synthesize and secrete a complex mixture of structurally and functionally diverse extracellular matrix (ECM) molecules. In addition to acting as scaffolding for the organization and stability of tissues, ECM molecules regulate cell survival and behavior. Research in my laboratory is focused on using the genetic tractability of the fruit fly Drosophila melanogaster to investigate the contribution of SPARC (Secreted Protein, Acidic, Rich in Cysteine) during embryo development. SPARC is a collagen-binding ECM protein with diverse biological activities. Our studies with Drosophila indicate that SPARC co-localizes with collagen IV in embryonic basal laminae. A basal lamina is a thin sheet of specialized ECM that separates epithelial cells from underlying connective tissue. The interaction of epithelial cells with basal laminae is critical for epithelial cell functions and connective tissue stability. The loss of SPARC expression leads to death during embryonic development due to decreased basal laminae stability and failure of the nervous system to form. We have generated a series of flies that express mutant SPARC using recent advances in genome engineering for the purpose of determining which domain/portion of SPARC is responsible for the embryonic defects. Since a direct interaction between SPARC and collagen IV in basal laminae has been demonstrated in vitro, we are carrying out studies to determine if SPARC and collagen IV interact in vivo. Our data indicate that the neural defects are due to compromised Notch-Delta signaling in the absence of SPARC, underscoring how signal transduction during development is regulated by ECM molecules.

受精后不久，多细胞生物合成并分泌结构和功能多样的细胞外基质（ECM）分子的复杂混合物。除了充当组织的组织和稳定性的支架外，ECM分子还调节细胞存活和行为。在我的实验室研究的重点是使用果蝇的遗传易处理性黑腹果蝇（Drosophila melanogaster），以调查在胚胎发育过程中的贡献分泌蛋白（分泌蛋白，酸性，富含半胱氨酸）。 SPARC是一种具有多种生物活性的胶原蛋白结合ECM蛋白。我们对果蝇的研究表明，在胚胎基底层中，cytoplasm与IV型胶原共定位。基底层是将上皮细胞与下面的结缔组织分开的专门ECM的薄片。上皮细胞与基底层的相互作用对于上皮细胞功能和结缔组织稳定性至关重要。在胚胎发育过程中，由于基底层稳定性降低和神经系统形成失败，EST 1表达的丧失导致死亡。我们已经产生了一系列的苍蝇，表达突变体的基因组工程的最新进展，以确定哪个域/部分的基因是负责胚胎缺陷。由于在体外已经证明了在基底层中的胶原蛋白和IV型胶原蛋白之间的直接相互作用，我们正在进行研究，以确定胶原蛋白和IV型胶原蛋白是否在体内相互作用。我们的数据表明，神经缺陷是由于Notch-Delta信号转导在缺乏ECM的情况下受损，强调了发育过程中的信号转导如何受到ECM分子的调节。