Key result
fhlA limits cardiac chamber size by restricting cell number in zebrafish embryos.
Why the study?
The roles of four-and-a-half LIM proteins FHL1-3, particularly fhlA, in heart development remain unclear.
The fhlA gene plays a crucial role in regulating heart chamber size during embryonic development by controlling the number of cardiac cells, a process likely regulated by retinoic acid signaling.
No direct clinical implications; leaves open fhlA's role in human cardiac development.
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.
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Xie et al. (2013) studied Heart chamber development. fhlA knockdown and overexpression vs. Controls was evaluated on Heart chamber size and cardiac cell number. In zebrafish embryos, fhlA regulates the size of the heart chamber by reducing the number of cardiac cells, with knockdown causing enlarged chambers and overexpression reducing chamber size.
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