THE RELATIONSHIP BETWEEN FOREGUT AND CARDIAC MORPHOGENESIS

University Of Kansas Medical Center, Kansas City KS

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The overall objective of the proposed work is to define the role of foregut morphogenesis in concomitant cardiac morphogenesis, at developmental stages when these two tubular organs are forming at the embryonic midline. Specifically, we seek to determine the role of endodermal folding in the movements that bring the bilateral cardiac precursors to the midline to form a tubular heart, comprised of an outer myocardial layer and an inner endocardial layer separated by a layer of extracellular matrix (ECM). Following heart tube fusion, the cardiac tube remains transiently open to and in contact with the ventral foregut. We have shown that components of the tubular heart (myocadial cells, endocardial cells, ECM constituents) are brought to the midline. In the context of the developing embryo, cellular movement can be seen as a net result of: 1) directed cell autonomous motility (migration relative to the cellular environment) and 2) large-scale displacements/deformations of the tissue. We seek to perturb both tissue movements and cell myocardial cell autonomous motility and to observe the resulting foregut and cardiac phenotypes using time-lapse recordings. Subsequent computational analyses will allow us to quantify cell autonomous motility, in vivo, under experimentally perturbed conditions. Proposed aims are as follows: Aim 1: To disrupt regression of the anterior intestinal portal/AIP (and thus foregut elongation) and to monitor dynamically (3D+time=4D) effects on heart morphogenesis during heart tube fusion (HH9-10). Aim 2: To determine if FGF, expressed in the precardiac mesoderm and/or adjacent endoderm, has an effect on cell motility during precardiac cell midline-migration and/or heart tube fusion. The long-term goal of this work is to determine if foregut and cardiac morphogenesis can be uncoupled, and to define what role foregut formation plays in formation of a tubular heart. Data obtained on which cell populations exhibit active cell motility and what role tissue-level displacements play will be used in future efforts to model avian heart tube formation.