Author's School

School of Engineering & Applied Science

Author's Department/Program

Biomedical Engineering

Language

English (en)

Date of Award

1-1-2011

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Chair and Committee

Larry Taber

Abstract

The heart is the first functioning organ to form in the embryo. For decades, biologists have worked to identify many of the genetic and molecular factors involved in heart development, and over the years, these efforts have helped elucidate the vast biochemical signaling networks, which drive cardiac specification and differentiation in the embryo. Still, the biophysical mechanisms which link these molecular factors to actual, physical changes in cardiac morphology remain unclear. The aim of this thesis is to identify some of the mechanical forces which drive heart tube assembly in the early chick embryo. A unique feature of this work is the combination of mathematical modeling with ex ovo culture experiments. Head fold formation is the first step in this process. It sets the stage for early cardiac development by folding the: initially flat) heart fields out-of-plane, enabling them to form a tube along the ventral side of the embryo. Here, we show that head fold formation is driven by forces that originate in the ectoderm, forces that are typically associated with neurulation --- the formation of the neural tube. The primitive heart tube itself then forms as these bilateral heart fields move toward the midline and fuse to construct a straight, muscle-wrapped tube. We show that the endoderm plays a crucial mechanical role during this process. Instead of just serving as a passive, secretory substrate for the crawling mesodermal heart fields, the endoderm actively contracts to pull the heart fields toward the midline. We then investigate how this endodermal contraction is spatially distributed, and how different distributions of contraction might affect the observed morphogenetic deformations during heart tube formation. Our methods can be readily generalized to other morphogenetic processes, enabling us to investigate how physical forces are organized at the tissue-level to create biological form.

Comments

Permanent URL: http://dx.doi.org/10.7936/K7X0651D

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