Leukemia‐associated transcription factor mllt3 is important for primitive erythroid development in zebrafish embryogenesis

Abstract

Background: MLLT3 (AF9) is a nuclear transcription factor crucial for hematopoietic stem cell and progenitor cell maintenance, but its role during embryonic hematopoiesis remains uncertain. Here, we examine the role of mllt3 in developmental hematopoiesis during embryogenesis using zebrafish.Results: Cloning, sequencing, phylogenetic, and synteny analyses showed high evolutionary conservation between important functional domains of the zebrafish orthologue of mllt3 and MLLT3 in humans. Quantitative reverse transcription-PCR and in situ hybridization analyses revealed that mllt3 is maternally supplied and zygotically expressed throughout embryonic development, and that expression is highest between 10 and 24 hours postfertilization (hpf) coincident with enrichment in the intermediate cell mass (ICM) and posterior blood island, which are the sites of the primitive and transient definitive hematopoiesis in zebrafish, respectively. Further, we found co-expression of mllt3 with the early hematopoietic progenitor markers tal1, gata2, and gata1a in the posterior ICM. By investigating zebrafish hematopoietic mutants, we discovered that mllt3 is involved in erythroid precursor formation. By 48-72 hpf, mllt3 expression proved to be restricted to non-hematopoietic tissues including head structures, pronephric tubules, and liver primordium. Conclusions: These findings establish a link between mllt3 and primitive erythropoiesis and provide the basis for future functional investigations.

Characterization and Comparative Analysis of Whole-Transcriptome Sequencing in High- and Low-Fecundity Chongming White Goat Ovaries during the Estrus Phase

“…ADSS1 is a key enzyme for guanine nucleotide de novo synthesis and is involved in converting IMP (inosinmonophosphat) to GMP; the cyclic form of GMP was shown to be associated with preparing the oocyte for fertilization and reproductive success [30]. MLLT3 functions as a transcription activator, elongates the transcription of target genes, and remodels chromatin in embryogenesis [31]. MLLT3 has also been reported to play essential roles in embryonic development, for instance, modifying histone H3K79 to affect cerebral cortex development [32].…”

Developmental regulation of primitive erythropoiesis

“…3). Zebrafish mllt3 has now been suggested to play a role in primitive erythropoiesis [70]. Its expression in the ICM colocalizes with that of other transcription factors known to regulate primitive erythropoiesis, including scl , gata2 and gata1a .…”