The multi-faceted role of Gata3 in developmental haematopoiesis

Abstract

The transcription factor Gata3 is crucial for the development of several tissues and cell lineages both during development as well as postnatally. This importance is apparent from the early embryonic lethality following germline Gata3 deletion, with embryos displaying a number of phenotypes, and from the fact that Gata3 has been implicated in several cancer types. It often acts at the level of stem and progenitor cells in which it controls the expression of key lineage-determining factors as well as cell cycle genes, thus being one of the main drivers of cell fate choice and tissue morphogenesis. Gata3 is involved at various stages of haematopoiesis both in the adult as well as during development. This review summarizes the various contributions of Gata3 to haematopoiesis with a particular focus on the emergence of the first haematopoietic stem cells in the embryo-a process that appears to be influenced by Gata3 at various levels, thus highlighting the complex nature of Gata3 action.

Keywords: Gata3; development; haematopoiesis.

Figure 1.

Gata3 expression in the AGM region. Images show cryosections of Gata3^+/Lz [114] E11.5 embryos stained with X-Gal for β-galactosidase activity (blue) and counterstained with Neutral Red. Ao, aorta; MD, mesonephric duct; Mes, mesenchyme; SNS, sympathetic nervous system; asterisks indicate Gata3 staining underneath haematopoietic clusters; arrowheads point to individual Gata3-expressing endothelial cells.

Figure 2.

Gata2 expression in Gata3 wild-type (WT) and knockout (KO) AGMs. Images of in situ hybridization with a Gata2 riboprobe on cryosections from E11.5 Gata3^+/+ (left) and Gata3^−/− [21] (right) embryos. Ao, aorta; MD, mesonephric duct; SNS, sympathetic nervous system.

Figure 3.

Gata3 involvement in AGM haematopoiesis. Schematic diagram of a transverse section through an E11.5 AGM region, highlighting the cell compartments that express Gata3. Gata3-positive cells (green) are found within the endothelial layer (yellow) of the dorsal aorta (Ao), in the mesonephric duct (MD), within the subaortic mesenchyme (orange; Mes) and in the sympathetic nervous system (SNS). Blood cells are shown in red. The light green cell depicts the putative involvement of Gata3 in the endothelial-to-haematopoietic transition. Curly arrows illustrate contributions made by the different components of the microenvironment to EHT/HSC support, of which only catecholamines are currently known to be Gata3-dependent. UGR, urogenital ridges.