Examining the mechanisms and roles of biologically generated forces in coordinating zebrafish development
Abstract/Contents
- Abstract
- Tissue function relies on proper specification of both cell type and cellular organization. For example, the heart requires properly differentiated myocytes to contract and pump blood. Additionally, the heart also requires properly constructed chambers and valves to maintain blood flow and oxygenate entire animals. Until recently, the study of biology has mainly focused on generating the correct cell type by exposing cells to specific biochemical stimuli. However, recently, studies have shown that physical forces are also central to cellular decisions and also influence collective cell migration. While some progress has been made in understanding how physical forces influence cell signaling, very little is known about how physical forces may help shape structure formation in multicellular development. In the work presented below, we demonstrate that a simple line tension provided by a contractile ring of actin and myosin helps reorient the blastoderm in the zebrafish embryo to the nearest long axis thus positioning the head-tail axis along the nearest axis of symmetry. We further provide analytical models and simulations, based on a simple force balance, that quantitatively account for the effect of this line tension during blastoderm migration. From these analyses, we present a dimensionless quantity that can be used to determine whether a biological system has generated sufficient coordinating force to influence its structure during development. We provide further evidence showing that external mechanical forces can profoundly affect biochemical signaling processes that control the location and orientation of the dorsoventral axis. In particular, we describe findings indicating that [beta]-catenin activation, a signaling event crucial to many biological processes, is sensitive to mechanical cues as well as extracellular Ca2+. In the last section, we provide an analytical framework that describes how mechanical forces may be transduced over long length and time scales. From these experiments and analyses, we observe that mechanical force plays an integral role in coordinating biological processes in development. We also observe that the organisms and cells may employ simple mechanisms to achieve mechanotransduction over large time and length scales. Finally, we demonstrate that mechanical perturbation can be a useful tool for probing biochemical pathways that can be difficult to achieve via chemical signals.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2015 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Chai, Jack |
|---|---|
| Associated with | Stanford University, Department of Chemical Engineering. |
| Primary advisor | Dunn, Alexander Robert |
| Thesis advisor | Dunn, Alexander Robert |
| Thesis advisor | Fuller, Gerald G |
| Thesis advisor | Talbot, William |
| Advisor | Fuller, Gerald G |
| Advisor | Talbot, William |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Jack Chai. |
|---|---|
| Note | Submitted to the Department of Chemical Engineering. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2015. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2015 by Jack Chai
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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