BMP signaling restricts hemato-vascular development from lateral mesoderm during somitogenesis

Gupta, Sourabh; Zhu, Min; Zon, Leonard I.; Evans, Todd

doi:10.1242/dev.02386

Cited by 50 publications

(39 citation statements)

References 55 publications

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“…Furthermore, when BMP signaling was disrupted in lateral mesoderm in the zebrafish model, by targeting a dominant-negative BMP receptor to Lmo2 þ cells, it was concluded that BMP signaling continues to function in the regulation of lineage specification after lateral mesoderm commitment. 57 However, at this stage, BMP signaling functions to restrict hemato-vascular fate in favor of pro-nephric development, 57 indicating that the effect of BMP signaling on hematopoiesis is affected by the exact stage of development. Moreover, in both murine and human embryonic stem cells, exposure to BMP4 has been reported to induce mesoderm formation, including hematopoietic commitment.…”

Section: Bmp Signaling In Hematopoietic Developmentmentioning

confidence: 99%

The role of Smad signaling in hematopoiesis and translational hematology

2011

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Hematopoietic stem cells (HSCs) reside in the bone marrow (BM) of adult individuals and function to produce and regenerate the entire blood and immune system over the course of an individual's lifetime. Historically, HSCs are among the most thoroughly characterized tissue-specific stem cells. Despite this, the regulation of fate options, such as self-renewal and differentiation, has remained elusive, partly because of the expansive plethora of factors and signaling cues that govern HSC behavior in vivo. In the BM, HSCs are housed in specialized niches that dovetail the behavior of HSCs with the need of the organism. The Smad-signaling pathway, which operates downstream of the transforming growth factor-b (TGF-b) superfamily of ligands, regulates a diverse set of biological processes, including proliferation, differentiation and apoptosis, in many different organ systems. Much of the function of Smad signaling in hematopoiesis has remained nebulous due to early embryonic lethality of most knockout mouse models. However, recently new data have been uncovered, suggesting that the Smad-signaling circuitry is intimately linked to HSC regulation. In this review, we bring the Smad-signaling pathway into focus, chronicling key concepts and recent advances with respect to TGF-b-superfamily signaling in normal and leukemic hematopoiesis.

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Section: Bmp Signaling In Hematopoietic Developmentmentioning

confidence: 99%

The role of Smad signaling in hematopoiesis and translational hematology

2011

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“…The control of Bmp dose is vital for normal development of the various mesodermal compartments and also for normal hematopoiesis (27). However, although Smads in general play an essential role in hematopoiesis (reviewed in ref.…”

Section: Bmp4mentioning

confidence: 99%

The SCL transcriptional network and BMP signaling pathway interact to regulate RUNX1 activity

Pimanda

Donaldson

Bruijn

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

109

104

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Hematopoietic stem cell (HSC) development is regulated by several signaling pathways and a number of key transcription factors, which include Scl/Tal1, Runx1, and members of the Smad family. However, it remains unclear how these various determinants interact. Using a genome-wide computational screen based on the well characterized Scl ؉19 HSC enhancer, we have identified a related Smad6 enhancer that also targets expression to blood and endothelial cells in transgenic mice. Smad6, Bmp4, and Runx1 transcripts are concentrated along the ventral aspect of the E10.5 dorsal aorta in the aorta-gonad-mesonephros region from which HSCs originate. Moreover, Smad6, an inhibitor of Bmp4 signaling, binds and inhibits Runx1 activity, whereas Smad1, a positive mediator of Bmp4 signaling, transactivates the Runx1 promoter. Taken together, our results integrate three key determinants of HSC development; the Scl transcriptional network, Runx1 activity, and the Bmp4/Smad signaling pathway.hematopoiesis ͉ SMAD6 ͉ hematopoietic stem cell ͉ aorta-gonad-mesonephros ͉ bioinformatics T he coordinated expression of genes lies at the heart of metazoan development, with complex gene-regulatory networks governing the spatial variation and temporal sequence with which genes are expressed (reviewed in ref. 1). Transcription factors and the cis-regulatory sequences to which they bind form the building blocks of gene-regulatory networks (2). Recognizing the components and hierarchy of gene-regulatory networks and their interactions with cell-signaling pathways not only provides insights into biology but also is fundamental to understanding how deregulation of networks contributes to pathology.In the postgenomics era, classical methods to screen for potential gene-regulatory regions, such as DNase I hypersensitivity mapping by Southern blotting of selected loci, are being superseded by new genome-wide techniques such as ChIP coupled to genomic tiling arrays (ChIP/chip) (3)or high-throughput sequencing of sequence tags indicating DNase I hypersensitivity (4). Although these largescale screening techniques may rapidly identify the positions of large numbers of candidate regulatory elements, they do not accurately predict their function, i.e., whether a given element is an enhancer or silencer, nor the pattern of activity in cell types other than those analyzed. Moreover, the large amounts of biological material required prevent use of these techniques in the study of early developmental programs and adult stem cell systems. Consequently, in silico approaches are increasingly used to perform genome-wide identification of candidate regulatory elements. Transcription factors often act as components of multiprotein complexes binding to clusters of binding sites. Well characterized regulatory modules with known combinations of transcription factor-binding sites can greatly facilitate the in silico prediction of other cis-regulatory modules that may be important in regulating the same biological process. This method is proving to be a powerful tool in ...

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“…However, recent gain-or lossof-function manipulation of the BMP signal pathway during middle or late gastrulation or even post-gastrulation suggested that BMP signaling also functions in blood fate specification (19,21,(41)(42)(43)(44)(45). Overall, our genetic data suggest that scube1 may regulate the BMP signaling for its later role during somitogenesis in the specification of blood progenitors.…”

Section: Discussionmentioning

confidence: 60%

Zebrafish scube1 (Signal Peptide-CUB (Complement Protein C1r/C1s, Uegf, and Bmp1)-EGF (Epidermal Growth Factor) Domain-containing Protein 1) Is Involved in Primitive Hematopoiesis

Tsao

Lee

et al. 2013

Journal of Biological Chemistry

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Background: Roles of zebrafish scube1 in primitive hematopoiesis remain unknown. Results: scube1 knockdown by morpholino-oligonucleotides reduced the expression of marker genes associated with primitive hematopoiesis. Conclusion: scube1 is critical for and acts at the top of the regulatory hierarchy of primitive hematopoiesis by modulating BMP signaling. Significance: Scube1 is a key regulator for primitive hematopoiesis in vertebrates.

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BMP signaling restricts hemato-vascular development from lateral mesoderm during somitogenesis

Cited by 50 publications

References 55 publications

The role of Smad signaling in hematopoiesis and translational hematology

The role of Smad signaling in hematopoiesis and translational hematology

The SCL transcriptional network and BMP signaling pathway interact to regulate RUNX1 activity

Zebrafish scube1 (Signal Peptide-CUB (Complement Protein C1r/C1s, Uegf, and Bmp1)-EGF (Epidermal Growth Factor) Domain-containing Protein 1) Is Involved in Primitive Hematopoiesis

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