simulating the mammalian blastocyst - molecular and mechanical interactions pattern the embryo模拟哺乳动物胚胎囊胚u2014u2014分子和机械的相互作用模式.pdfVIP

Simulating the Mammalian Blastocyst - Molecular and Mechanical Interactions Pattern the Embryo 1 2 1,3 Pawel Krupinski , Vijay Chickarmane , Carsten Peterson * 1 Computational Biology Biological Physics, Department of Astronomy and Theoretical Physics, Lund University, Lund, Sweden, 2 Division of Biology, California Institute of Technology, Pasadena, California, United States of America, 3 Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden Abstract Mammalian embryogenesis is a dynamic process involving gene expression and mechanical forces between proliferating cells. The exact nature of these interactions, which determine the lineage patterning of the trophectoderm and endoderm tissues occurring in a highly regulated manner at precise periods during the embryonic development, is an area of debate. We have developed a computational modeling framework for studying this process, by which the combined effects of mechanical and genetic interactions are analyzed within the context of proliferating cells. At a purely mechanical level, we demonstrate that the perpendicular alignment of the animal-vegetal (a-v) and embryonic-abembryonic (eb-ab) axes is a result of minimizing the total elastic conformational energy of the entire collection of cells, which are constrained by the zona pellucida. The coupling of gene expression with the mechanics of cell movement is important for formation of both the trophectoderm and the endoderm. In studying the formation of the trophectoderm, we contrast and compare quantitatively two hypotheses: (1) The position determines gene expression, and (2) the gene expression determines the position. Our model, which couples gene expressi