The roles and controls of GATA factors in blood and cardiac development

Abstract

GATA factors play central roles in the programming of blood and cardiac cells during embryonic development. Using the experimentally accessible Xenopus and zebrafish models, we report observations regarding the roles of GATA-2 in the development of blood stem cells and GATA-4, -5, and -6 in cardiac development.We show that blood stem cells develop from the dorsal lateral plate mesoderm and GATA-2 is required at multiple stages. Firstly, GATA-2 is required to make the cells responsive to VEGF-A signalling by driving the synthesis of its receptor, FLK-1/KDR. This leads to differentiation into the endothelial cells that form the dorsal aorta. GATA-2 is again required for the endothelial-to-haematopoietic transition that takes place later in the floor of the dorsal aorta. GATA-2 expression is dependent on BMP signalling for each of these inputs into blood stem cell programming.GATA-4, -5, and -6 work together to ensure the specification of cardiac cells during development. We have demonstrated redundancy within the family and also some evolution of the functions of the different family members. Interestingly, one of the features that varies in evolution is the timing of expression relative to other key regulators such as Nkx2.5 and BMP. We show that the GATA factors, Nkx2.5 and BMP regulate each other and it would appear that what is critical is the mutually supportive network of expression rather than the order of expression of each of the component genes. InXenopus and zebrafish, the cardiac mesoderm is adjacent to an anterior population of cells giving rise to blood and endothelium. This population is not present in mammals and we have shown that, like the cardiac population, the blood and endothelial precursors require GATA-4, -5, and -6 for their development. Later, blood-specific or cardiacspecific regulators determine the ultimate fate of the cells, and we show that these regulators act cross-antagonistically. Fibroblast growth factor (FGF) signalling drives the cardiac fate, and we propose that the anterior extension of the FGF signalling field during Abbreviations: ALPM, anterior lateral plate mesoderm; ATAC-seq, assay for transposase-accessible chromatin-sequencing; BMP, bone morphogenetic

Teratogenic and Neurotoxic Effects of n‐Butanol on Zebrafish Development

“…In this study, when the teratogenic effects of n‐butanol on the embryos and larvae of Zebrafish were examined, we found that the highest rate of malformation was for cardiac edema. At high doses of n‐butanol (500, 750, and 1,000 mg/L), cardiac edema was observed to circulate in the tail vein and artery veins of larvae at 96 h; thus, we assume that endothelial cells in the vessels are affected by n‐butanol and cause cardiac edema (Jiang et al 2017; Ku et al 2017; Dobrzycki et al 2020). Similarly, high doses of n‐butanol (500, 750, and 1,000 mg/L) are thought to cause abnormalities in heart morphology and decrease heart rate, stopping blood circulation and weakening the heart muscle and causing inadequate blood pressure in the vein (Tanaka et al 2016; Walton et al 2019).…”

Exploring the Expression of Cardiac Regulators in a Vertebrate Extremophile: The Cichlid Fish Oreochromis (Alcolapia) alcalica

“…In zebrafish, however, MO knockdown of gata5 and gata6 resulted in cardia bifida and substantial reduction in expression of contractile protein genes, whereas gata4 morphant cardiomyocytes migrated to the midline normally [ 74 ]. The difference in phenotype severity of gata5 morphants in Xenopus and zebrafish suggests a change in the activity of these GATA factors during evolution [ 75 ].…”

From Stripes to a Beating Heart: Early Cardiac Development in Zebrafish

“…Mutants affecting FGF signaling have been among the earliest isolated heart anomalies in zebrafish, as illustrated with the mutant for fgf8 ( ace ) that features predominant ventricle defects [ 54 ]. FGF signaling is deployed at various stages during mesoderm and cardiovascular fate patterning, starting with dorso-ventral patterning during gastrulation, to drive cardiac fate and restrict anterior endothelial-hematopoietic fates in early somitogenesis, and in controlling nkx2.5 and gata4 expression in cardiac precursors [ 54 , 105 , 106 , 107 ]. Perturbations of FGF signaling during the medial migration of the ALPM progenitors reduce ventricle size and inhibit BA formation, possibly suggesting a spatial or temporal sensitivity to FGF signaling in the anterior-posterior patterning of the OFT region [ 89 , 107 ].…”