Grant Details
Description
Proliferating cardiac myoblasts are observed in situ only during
a short developmental period in early embryogenesis, after which
all of the muscle cells of the myocardium - even the proliferating
cells - bear contractile elements and are partially differentiated.
Since the partially differentiated cells possess only a limited
capacity for mitotic growth, replication of cardiac myocytes stops
soon after birth, leaving the myocardium with no significant
regenerative ability. The components of the embryonic
extracellular matrix in which cardiac myoblasts proliferate and
differentiate are quite different from those of fetal or adult
heart, and their composition and architecture are not well
understood. One reason is the limited amount of material available
for analysis at such an early developmental period. To fully
understand the induction of cardiac myogenesis, a better
understanding of the cellular and extracellular matrix components
of the embryonic heart is required. The purpose of this proposal
is to recreate in culture the earliest events of cardiac
organogenesis observed in the embryo. Based on in situ
observations, such culture systems should consist of three cellular
components: cardiac myoblasts, endodermal cells, and embryonic
endocardial cells. The extracellular matrix components should
include the basal lamina between the endoderm and the cardiac
myoblast and cardiac jelly found between the embryonic endocardium
and the cardiac myoblasts. In this proposal, culture equivalents
for all three cellular components will be characterized. Co-
culture experiments are proposed that will examine the inductive
interactions between these three embryonic cell types, and the
mechanisms that lead to the elaboration of the embryonic cardiac
matrices. Defined embryonic, fetal and adult extracellular
matrices then will be assembled in vitro, and their effects on the
phenotypes of cardiac myoblasts and myocytes will be elucidated.
By comparing the cellular and extracellular components of the
embryonic and adult heart, insights should be gained into the
forces that stifle regeneration of the myocardium.
Status | Finished |
---|---|
Effective start/end date | 05/1/90 → 04/30/93 |
Funding
- National Heart, Lung, and Blood Institute
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