Leukemia‐associated transcription factor mllt3 is important for primitive erythroid development in zebrafish embryogenesis. Issue 10 (2nd May 2022)

• Record Type: Journal Article
• Authors: Germano, Giuseppe; Porazzi, Patrizia; Felix, Carolyn A.
• Is Part Of: Developmental dynamics. Volume 251:Issue 10(2022)
• Page Start: 1728
• Page End: 1740
• Publication Date: 2022-05-02
• Subjects: gene expression -- intermediate cell mass -- mutants -- primitive hematopoiesis; Morphogenesis -- Periodicals; Anatomy -- Periodicals; Anatomie -- Périodiques; Biologie du développement -- Périodiques; 571.833
• DOI: 10.1002/dvdy.477
• Languages: English
• ISSNs: 1058-8388

Abstract

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 post‐fertilization (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. Key Findings: Identification and cloning of the full‐length cDNA zebrafish ortholog of the human MLLT3 gene. mllt3 is maternally suppled, dynamically and specifically expressed during embryo development. mllt3 is expressed in specific tissues including the intermediate cell mass (ICM) and posterior blood island (PBI). mllt3 expression is associated with erythroid lineage formation