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A House with Many Rooms: How the Heart Got Its Chambers with foxn4
BJ Woolston
Salt Lake Community College
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Running Head: OVERVIEW OF A HOUSE WITH MANY ROOMS TITLE PAGE
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Abstract
This paper is an overview of an article that describes how vertebrate and invertebrate hearts are
formed using foxn4. Descriptors of development and functions of the chambers of the heart are
described and evaluated. It discusses the atrioventricular (AV) canal as a part of the process. The
member of the forkhead box (fox) family is identified in this article. Foxn4 works with tbx5 to
direct development of the AV boundary by regulating tbx2b. The fox gene family is extremely
important to regulating cell specification, differentiation and proliferation during development of
the chambers.
Running Head: OVERVIEW OF A HOUSE WITH MANY ROOMS TITLE PAGE
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Overview of A House with Many Rooms:
How the Heart Got Its Chambers with foxn4
There are two lateral domains that fuse at the midline. This is where the vertebrate heart
is initially formed. There is a very simple heart tube formed here that is very similar to
invertebrate hearts (or dorsal vessels). Distinct chambers are formed after this simple heart
undergoes a series of morphogenetic rearrangements. The separation of the inflow (atrial) and
the outflow (ventricular) occur at the atrioventricular (AV) canal. Proper cardiac rhythm requires
unidirectional blood flow and electrical conduction system. This article describes findings of a
member of the forkhead box (fox) family of transcription factors foxn4, which is extremely
important to regulating cell specification, differentiation and proliferation during development of
the chambers.
The basic design of the cardiovascular system has changed with evolution due to
increased blood flow and pressure in vertebrates. Invertebrates have smaller surface-to-volume
ratios, which require less oxygenated blood. Drosophila promotes circulation of hemolymph, the
insect equivalent of blood, within an open circulatory system. Vertebrates need to have more
intricate circulatory loops that can provide oxygenated blood from the lungs or gills (gas
exchange organs) to the rest of the body as a whole as well as a return of the deoxygenated blood
to the heart. A two-chambered fish heart is the simplest form of unidirectional blood flow for a
vertebrate. The deoxygenated blood is returned through the atria then pumped through to the
ventricle. Once the ventricle is full, it contracts which forces the blood to the gills for
oxygenation before the blood moves on to the rest of the body.
There are three critical rolls that the AV boundary holds in successful unidirectional
blood flow. The first is that the cell shape changes within the AV boundary causes the heart tube
Running Head: OVERVIEW OF A HOUSE WITH MANY ROOMS TITLE PAGE
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to bend between the atrial and ventricular compartments, forming an actual restriction. Secondly,
the endocardial cells become endocardial cushions after migrating to the lumen. Third of all,
there are fewer gap junctions, which make sequential contractions of the atrial and ventricular
compartments possible.
Zebrafish and their heart’s development are used in this article to examine the affects of
the foxn4 on various mutations. The mutation slipjig (sli) had many defects exhibited in the
development, which lead to a higher risk of cardiovascular failure. The heart tube forms linearly
naturally but fails to bend due to the lack of cell shape changes. The endocardial cushions
develop abnormally as well. This shows that the foxn4 gene is useful in the AV boundary for
proper development.
In the sli/foxn4 phenotype observed and reported on in this article, the tbx2b expression
was lost in these mutants. Tbx genes have been directly correlated with proper cardiac
development for many years. Fox genes have repeatedly been shown helping to regulate the Tbx
genes during various stages of cardiac development.
This article believes that the foxn4 came into play to stimulate differentiation of the AV
canal during the evolutionary leap from the simple linear heart tubes incased in invertebrates to
the hearts with many chambers that vertebrates need for unidirectional blood flow. There has not
been a Fox gene found in early Drosophila, which supports the theory that foxn4 and other Fox
genes have played leading roles in proper AV boundary development for vertebrates.
Not all questions directed at the relationship between the Fox and Tbx genes are
answered in this article although it can be gathered that their correlation in proper cardiac
development is indeed important. The research shown in this article definitely shines some light
Running Head: OVERVIEW OF A HOUSE WITH MANY ROOMS TITLE PAGE
on how new chambers were developed to successfully pump oxygenated blood through them to
the body as a whole as well as return deoxygenated blood back to the heart.
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Running Head: OVERVIEW OF A HOUSE WITH MANY ROOMS TITLE PAGE
References
Cohen, E. D., &Morrisey, E. E. (2008) A house with many rooms: how the heart got its
chambers with foxn4. Genes Dev. 2008 22: 706-710
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