zfp36 expression delineates both myeloid cells and cells localized to the fusing neural folds in Xenopus tropicalis

Abstract

Regulatory RNA binding proteins allow for specific control of gene expression in a very dynamic manner. In mammals ZFP36, formerly known as Tristetraprolin, controls the inflammatory response by binding to an AU-rich element located in the 3' untranslated region of its target mRNAs. The developping embryo relies on a population of primitive macrophages to ensure proper immunity. Although the role of zfp36 in adult immunity has been extensively studied, its expression in the developing immune system has been poorly documented. Here, we have used whole mount in situ hybridization with a 3' UTR specific probe to address the expression of zfp36 in developing Xenopus tropicalis embryos. We have shown that zfp36 is expressed in two distinct cellular populations. First, it is a new marker of primititive myeloid cells, being coexpressed with the myeloid marker mpo. Therefore this early expression may suggest a role for zfp36 in macrophage differentiation and activation. In addition, a second cell population was found to transiently express zfp36, but not mpo, along the fusing neural folds and may correspond to cells undergoing autophagy during neural tube closure. KEY WORDS: RNA binding proteins, Xenopus tropicalis, embryonic immunityZFP36 formerly known as Tristetraprolin (TTP) (Lai et al., 2014) belongs to a family of RNA binding Zinc Fingers containing proteins which is composed of 3 members in humans, ZFP36, ZFP36L1 and ZFP36L2. In Xenopus laevis, a fourth member previously called C3H4 and named Zfp36L4 has been identified (Belloc and Méndez, 2008;De et al., 1999;Tréguer et al., 2013).Functionally, ZFP36 has been shown to regulate post-transcriptionnally the inflammatory response by controling the expression level of inflammatory factors such as TNF-alpha (Carballo et al., 1998) or GM-CSF (Carballo et al., 2000. Mice constitutively deficient for ZFP36, albeit apparently normal at birth develop a debilitating inflammatory response (Taylor et al., 1996). ZFP36 acts through the specific binding to AU-rich element present in the 3'UTR of the targeted mRNAs and triggers their destabilization .Extensive work has been conducted to address the function of ZFP36 in the regulation of inflammatory processes while its expression in the developing immune system has been loosely documented. Xenopus is a useful model system to study the multiple steps of early immune system development (Ciau-Uitz et al., 2010). In Xenopus embryos, primitive hematopoiesis is initiated in a ventral region termed the ventral blood island (VBI) that is the equivalent of the mammalian extraembryonic yolk sac. The Int. J. Dev. Biol. 58: 751-755 (2014) VBI is composed of two areas, the anterior VBI (aVBI) and the posterior VBI (pVBI) that give rises to different cell populations. The aVBI originates from blastomeres C1D1 and comprises an hemangioblast-like population of cells expressing both blood and endothelial cell markers at stage 14. Yet, it has recently been shown that in normal situation the aVBI will only produce blood cells (Myers a...

Knockdown of miR-128a induces Lin28a expression and reverts myeloid differentiation blockage in acute myeloid leukemia

“…Ectopic expression of Lin28A also significantly increased p21 protein levels ( P <0.001 at 24 h and P <0.05 at 48 h), inducing cell-cycle arrest in the S phase ( P <0.01 at 24 h and P <0.001 at 48 h) (Figures 2a and i). Consistent to the ability of Lin28A in inducing hematopoietic differentiation in AML cells, we detected a significant increase of EGR2 and ZFP36 , two key regulators of monocyte/macrophage differentiation (Figures 2j–k), 34, 35, 36 and ANXA1 , a gene normally stored in inside macrophage cytosol (Figure 2l) 37 after Lin28A overexpression at 24–48 h.…”