BMP-mediated specification of the erythroid lineage suppresses endothelial development in blood island precursors

Myers, Candace T.; Krieg, Paul A.

doi:10.1182/blood-2013-03-490045

Cited by 26 publications

(20 citation statements)

References 50 publications

(77 reference statements)

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“…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 and Krieg, 2013), the myeloid lineage being highly represented among those. These myeloid cells can be clearly distinguished by following the expression of a peroxidase family member, the myeloperoxidase (mpo also know as xpox2, (Smith et al, 2002)).…”

Section: Abstract: Rna Binding Proteins Xenopus Tropicalis Embryonmentioning

confidence: 99%

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

2014

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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...

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Section: Abstract: Rna Binding Proteins Xenopus Tropicalis Embryonmentioning

confidence: 99%

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

2014

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“…Bmps also function at later stages to prevent bipotential progenitors from choosing the endothelial rather than the erythroid lineage (Myers and Krieg, 2013). Bmps are believed to comprise part of the noncell-autonomous signal that is transmitted from the ectoderm to the mesoderm to enable it to form blood (Kumano et al, 1999;Maeno, 2003;Tran et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Tril targets Smad7 for degradation to allow hematopoietic specification in Xenopus embryos

et al. 2016

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In Xenopus laevis, Bone morphogenetic proteins induce expression of the transcription factor Gata2 during gastrulation, and Gata2 is required in both ectodermal and mesodermal cells to enable mesoderm to commit to a hematopoietic fate. In the current studies, we identify tril as a Gata2 target gene that is required in both ectoderm and mesoderm for primitive hematopoiesis to occur. Tril is a transmembrane protein that functions as a co-receptor for Toll like receptors to mediate innate immune responses in the adult brain, but developmental roles for this molecule have not been identified. We show that Tril function is required both upstream and downstream of Bmp receptor mediated Smad1 phosphorylation for induction of Bmp target genes. Mechanistically, Tril triggers degradation of the Bmp inhibitor, Smad7. Tril-dependent down regulation of Smad7 relieves repression of endogenous Bmp signaling during gastrulation and this enables mesodermal progenitors to commit to a blood fate. Thus, Tril is a novel component of a Bmp-Gata2 positive feedback loop that plays an essential role in hematopoietic specification.

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“…Studies of HSPC derivation from embryonic stem cells and induced pluripotent stem cells further support the idea that definitive HSC are derived from hemogenic endothelial cells, and early blood cells are independently fated [100,101]. Myers and Krieg present an elegant series of experiments, which suggest that the hemangioblast may be a state of competence rather than a bipotential progenitor state that exists in vivo [102].…”

Section: Role Of the Vascular Endothelium In Developmental Hematopoiesismentioning

confidence: 89%

Vascular Niche in HSC Development, Maintenance and Regulation

Coşkun

Hirschi

2015

Tissue-Specific Stem Cell Niche

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BMP-mediated specification of the erythroid lineage suppresses endothelial development in blood island precursors

Abstract: Key Points Commitment to the erythroid transcriptional program precludes endothelial development in a blood island precursor population.

Cited by 26 publications

References 50 publications

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

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

Tril targets Smad7 for degradation to allow hematopoietic specification in Xenopus embryos

Vascular Niche in HSC Development, Maintenance and Regulation

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