Four-and-a-half LIM proteins FHL1-3 play important roles in cardiovascular pathophysiology.
However, their roles in heart development remain unclear. Here, we report that fhlA, the zebrafish homolog of
human FHL1, was found to be expressed around the 22-somite stage. After 24 hpf, expression was restricted
to the heart. fhlA knockdown caused an enlarged cardiac chamber phenotype with up-regulated expression of
the cardiac markers, but fhlA overexpression reduced the sizes of the cardiac chambers and down-regulated
expression of the markers. The morphology associated with the cmlc2, amhc, and vmhc expression patterns at
the 22 somite and 24 hpf stages included a broadened domain in embryos lacking fhlA and a smaller domain
in embryos overexpressing fhlA. The changes in the sizes of the chambers were attributed to the changes in
the number of ventricular and atrial cells. Loss of fhlA caused a longer heart period and pause between
heartbeats in M-modes than in controls, but fhlA overexpression caused shorter systolic and diastolic intervals.
Abnormal cardiac chambers and physiological function were found to be largely rescued. We also showed the
expression of fhlA in the heart to be increased by retinoic acid (RA) and decreased by the RA synthase
inhibitor DEAB. Both fhlA and RA signaling caused a phenotype characterized by the morphological alterations
in the chamber sizes, suggesting that the role of fhlA in heart development is probably regulated by RA
signaling. Taken together, these results showed that fhlA regulates the size of the heart chamber by reducing
the number of cardiac cells.
Keywords: Cardiomyocytes, development, fhlA, heart chamber, physiological function, retinoic acid signaling.
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