BMP2 is a positive regulator of Nodal signaling during left-right axis formation in the chicken embryo

Development ◽  
2002 ◽  
Vol 129 (14) ◽  
pp. 3421-3429
Author(s):  
Thomas Schlange ◽  
Hans-Henning Arnold ◽  
Thomas Brand
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Target Genes ◽  
Bmp Signaling ◽  
Paraxial Mesoderm ◽  
Axis Formation ◽  
Nodal Signaling ◽  
Lateral Plate Mesoderm ◽  
Lateral Plate ◽  
Positive Regulator ◽  
The Right

A model of left-right axis formation in the chick involves inhibition of bone morphogenetic proteins by the antagonist Car as a mechanism of upregulating Nodal in the left lateral plate mesoderm. By contrast, expression of CFC, a competence factor, which is absolutely required for Nodal signaling in the lateral plate mesoderm is dependent on a functional BMP signaling pathway. We have therefore investigated the relationship between BMP and Nodal in further detail. We implanted BMP2 and Noggin-expressing cells into the left lateral plate and paraxial mesoderm and observed a strong upregulation of Nodal and its target genes Pitx2 and Nkx3.2. In addition Cfc, the Nodal type II receptor ActrIIa and Snr were found to depend on BMP signaling for their expression. Comparison of the expression domains of Nodal, Bmp2, Car and Cfc revealed co-expression of Nodal, Cfc and Bmp2, while Car and Nodal only partially overlapped. Ectopic application of BMP2, Nodal, and Car as well as combinations of this signaling molecules to the right lateral plate mesoderm revealed that BMP2 and Car need to synergize in order to specify left identity. We propose a novel model of left-right axis formation, which involves BMP as a positive regulator of Nodal signaling in the chick embryo.

scholarly journals Multi-modal effects of BMP signaling on Nodal expression in the lateral plate mesoderm during left–right axis formation in the chick embryo

2013 ◽  
Vol 374 (1) ◽  
pp. 71-84 ◽  
Author(s):  
Kenjiro Katsu ◽  
Norifumi Tatsumi ◽  
Daisuke Niki ◽  
Ken-ichi Yamamura ◽  
Yuji Yokouchi
Keyword(s):  
Chick Embryo ◽  
Bmp Signaling ◽  
Axis Formation ◽  
Lateral Plate Mesoderm ◽  
Lateral Plate

BMP signaling positively regulates Nodal expression during left right specification in the chick embryo

Development ◽  
2002 ◽  
Vol 129 (14) ◽  
pp. 3431-3440 ◽  
Author(s):  
M. Elisa Piedra ◽  
Mana A. Ros
Keyword(s):  
Bmp Signaling ◽  
Lateral Plate Mesoderm ◽  
Lateral Plate ◽  
Positive Role ◽  
Molecular Control ◽  
Left And Right ◽  
Left Right Asymmetry ◽  
The Right ◽  
Rapid Activation ◽  
Positive Effect

Exogenous application of BMP to the lateral plate mesoderm (LPM) of chick embryos at the early somite stage had a positive effect on Nodal expression. BMP applications into the right LPM were followed by a rapid activation of Nodal, while applications into the left LPM resulted in expansion of the normal domain of Nodal expression. Conversely, blocking of BMP signaling by Noggin in the left LPM interfered with the activation of Nodal expression. These results support a positive role for endogenous BMP on Nodal expression in the LPM. We also report that BMP positively regulates the expression of Caronte, Snail and Cfc in both the left and right LPM. BMP-treated embryos had molecular impairment of the midline with downregulation of Lefty1, Brachyury and Shh but we also show that the midline defect was not sufficient to induce ectopic Nodal expression. We discuss our findings in the context of the known molecular control of the specification of left-right asymmetry.

scholarly journals Primary cilium polarity: morphogenetic consequences.

2018 ◽  
Author(s):  
Marco Regolini
Keyword(s):  
Primary Cilia ◽  
Break Symmetry ◽  
Otic Vesicle ◽  
Nodal Signaling ◽  
Lateral Plate Mesoderm ◽  
Cell Orientation ◽  
Lateral Plate ◽  
Situs Solitus ◽  
Left And Right ◽  
Breaking Symmetry

In zebrafish inner ear, hair cell orientation in anterior and posterior maculae of the embryonic otic vesicle is different (about 30-40 degrees): this is rather unusual in planar polarity mechanism of action, instead suggests that kinocilia may be rotationally polarized. In mice node, the innermost monociliated cells generate a left-ward fluid flow sensed by the immotile primary cilia of Left peri-nodal cells: the Nodal signaling pathway is then expressed asymmetrically, in the Left lateral plate mesoderm, breaking symmetry in visceral organs (situs solitus); however, Right peri-nodal cells also, if artificially excited by a right-ward flow, break symmetry and activate the Nodal cascade, though inverting visceral organ asymmetry (situs inversus); surprisingly, peri-nodal cells prove to be adept at distinguishing flow directionality. Recently, in the Kupffer vesicle (the zebrafish laterality organ), chiral primary cilia orientation has been described: primary cilia, in the left and right side, are symmetrically oriented, showing a mirror average divergence of about 15-20 degrees from the midline. This finding, taken together with the mirror behavior of mouse perinodal cells and zebrafish hair cells, champions the idea of primary cilia enantiomerism.

scholarly journals Gdf3 is required for robust Nodal signaling during germ layer formation and left-right patterning

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Jose L Pelliccia ◽  
Granton A Jindal ◽  
Rebecca D Burdine
Keyword(s):  
Embryonic Development ◽  
Nodal Signaling ◽  
Lateral Plate Mesoderm ◽  
Embryonic Patterning ◽  
Lateral Plate ◽  
Mesoderm Formation ◽  
Germ Layer Formation ◽  
Multiple Stages ◽  
Tgfβ Superfamily

Vertebrate embryonic patterning depends on signaling from Nodal, a TGFβ superfamily member. There are three Nodal orthologs in zebrafish; southpaw directs left-right asymmetries, while squint and cyclops function earlier to pattern mesendoderm. TGFβ member Vg1 is implicated in mesoderm formation but the role of the zebrafish ortholog, Growth differentiation factor 3 (Gdf3), has not been fully explored. We show that zygotic expression of gdf3 is dispensable for embryonic development, while maternally deposited gdf3 is required for mesendoderm formation and dorsal-ventral patterning. We further show that Gdf3 can affect left-right patterning at multiple stages, including proper development of regional cell morphology in Kupffer’s vesicle and the establishment of southpaw expression in the lateral plate mesoderm. Collectively, our data indicate that gdf3 is critical for robust Nodal signaling at multiple stages in zebrafish embryonic development.

scholarly journals Dermomyotome-derived endothelial cells migrate to the dorsal aorta to support hematopoietic stem cell emergence

2020 ◽  
Author(s):  
Pankaj Sahai-Hernandez ◽  
Claire Pouget ◽  
Ondřej Svoboda ◽  
David Traver
Keyword(s):  
Endothelial Cells ◽  
Stem Cell ◽  
Paraxial Mesoderm ◽  
Dorsal Aorta ◽  
Similar Process ◽  
Lateral Plate Mesoderm ◽  
Lateral Plate ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells ◽  
Endothelial Precursors

AbstractDevelopment of the dorsal aorta is a key step in the establishment of the adult blood-forming system, since hematopoietic stem and progenitor cells (HSPCs) arise from ventral aortic endothelium in all vertebrate animals studied. Work in zebrafish has demonstrated that arterial and venous endothelial precursors arise from distinct subsets of lateral plate mesoderm. Earlier studies in the chick showed that paraxial mesoderm generates another subset of endothelial cells that incorporate into the dorsal aorta to replace HSPCs as they exit the aorta and enter circulation. Here we show that a similar process occurs in the zebrafish, where a population of endothelial precursors delaminates from the somitic dermomyotome to incorporate exclusively into the developing dorsal aorta. Whereas somite-derived endothelial cells (SDECs) lack hematopoietic potential, they act as local niche to support the emergence of HSPCs from neighboring hemogenic endothelium. Thus, at least three subsets of endothelial cells (ECs) contribute to the developing dorsal aorta: vascular ECs, hemogenic ECs, and SDECs. Taken together, our findings indicate that the distinct spatial origins of endothelial precursors dictate different cellular potentials within the developing dorsal aorta.

scholarly journals Selective disruption of synaptic BMP signaling by a Smad mutation adjacent to the highly conserved H2 helix

2019 ◽  
Author(s):  
Tho Huu Nguyen ◽  
Tae Hee Han ◽  
Stuart Newfeld ◽  
Mihaela Serpe
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Target Genes ◽  
Normal Development ◽  
Single Point ◽  
Point Mutations ◽  
Bmp Signaling ◽  
Electrophysiological Properties ◽  
Molecular Features ◽  
Synaptic Junctions ◽  
And Function

ABSTRACTBone morphogenetic proteins (BMPs) shape normal development and function via canonical and non-canonical signaling pathways. When activating the canonical pathway, BMPs initiate signaling by binding to transmembrane receptors that phosphorylate pathway effectors, the Smad proteins, inducing their translocation into the nucleus and thus regulation of target genes. Phosphorylated Smads also accumulate at cellular junctions, but this non-canonical signaling modality remains less defined. We have recently reported that phosphorylated Smad (pMad in Drosophila) accumulates at synaptic junctions in complexes with genetically distinct composition and regulation. Here we examined a wide collection of Drosophila Mad alleles and searched for molecular features relevant to pMad accumulation at synaptic junctions. We found that strong Mad alleles generally disrupt both synaptic and nuclear pMad accumulation, whereas moderate Mad alleles have a wider range of phenotypes and could selectively impact different BMP signaling modalities. Interestingly, synaptic pMad appeared more sensitive to net reduction in Mad levels than nuclear pMad. Importantly, a previously uncharacterized allele, Mad8, showed markedly reduced synaptic pMad levels but only moderately diminished nuclear pMad signals. The postsynaptic composition and electrophysiological properties of Mad8 NMJs were similarly altered. Using biochemical approaches, we examined how single point mutations such as S359L, present in Mad8, could influence the Mad-receptor interface and we identified a key molecular determinant, the H2 helix. Our study highlights the biological relevance of the Smad-dependent, non-canonical BMP signaling and uncovers a highly conserved structural feature of Smads, critical for normal development and function.

scholarly journals Quantitative Imaging in Whole-mount Zebrafish Embryos Traces Morphogen Gradient Maintenance and Noise Propagation in BMP Signaling

2021 ◽  
Author(s):  
Xu Wang ◽  
Linlin Li ◽  
Ye Bu ◽  
Yixuan Liu ◽  
Tzu-Ching Wu ◽  
...  
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Single Molecule ◽  
Zebrafish Embryo ◽  
Quantitative Imaging ◽  
Bmp Signaling ◽  
Morphogen Gradient ◽  
Nodal Signaling ◽  
Embryonic Patterning ◽  
Whole Mount ◽  
Development Data

Abstract Dorsoventral (DV) embryonic patterning relies on precisely controlled interpretation of morphogen signaling. In all vertebrates, DV axis specification is informed by gradients of bone morphogenetic proteins (BMPs). We developed a 3D single-molecule mRNA quantification method in whole-mount zebrafish to quantify the inputs and outputs in this pathway. In combination with 3D computational modeling of zebrafish embryo development, data from this method revealed that sizzled (Szl), shaped by BMP and Nodal signaling, maintained a consistent inhibition level with chordin (Chd) to maintain the BMP morphogen gradient. Intriguingly, intrinsic BMP morphogen expression is highly noisy at the ventral marginal layer in the early zebrafish gastrula, where the gradient for DV patterning is established, which implies an unexpected role for noise in gradient shaping.

scholarly journals Hippo signaling determines the number of venous pole cells that originate from the anterior lateral plate mesoderm in zebrafish

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Hajime Fukui ◽  
Takahiro Miyazaki ◽  
Renee Wei-Yan Chow ◽  
Hiroyuki Ishikawa ◽  
Hiroyuki Nakajima ◽  
...  
Keyword(s):  
Cell Number ◽  
Bmp Signaling ◽  
Hippo Signaling ◽  
Lateral Plate Mesoderm ◽  
Cardiomyocyte Proliferation ◽  
Heart Tube ◽  
Lateral Plate ◽  
Large Tumor ◽  
Developmental Potential ◽  
Anterior Lateral Plate Mesoderm

The differentiation of the lateral plate mesoderm cells into heart field cells constitutes a critical step in the development of cardiac tissue and the genesis of functional cardiomyocytes. Hippo signaling controls cardiomyocyte proliferation, but the role of Hippo signaling during early cardiogenesis remains unclear. Here, we show that Hippo signaling regulates atrial cell number by specifying the developmental potential of cells within the anterior lateral plate mesoderm (ALPM), which are incorporated into the venous pole of the heart tube and ultimately into the atrium of the heart. We demonstrate that Hippo signaling acts through large tumor suppressor kinase 1/2 to modulate BMP signaling and the expression of hand2, a key transcription factor that is involved in the differentiation of atrial cardiomyocytes. Collectively, these results demonstrate that Hippo signaling defines venous pole cardiomyocyte number by modulating both the number and the identity of the ALPM cells that will populate the atrium of the heart.

The homeobox gene Pitx2: mediator of asymmetric left-right signaling in vertebrate heart and gut looping

Development ◽  
1999 ◽  
Vol 126 (6) ◽  
pp. 1225-1234 ◽  
Author(s):  
M. Campione ◽  
H. Steinbeisser ◽  
A. Schweickert ◽  
K. Deissler ◽  
F. van Bebber ◽  
...  
Keyword(s):  
Ectopic Expression ◽  
Homeobox Gene ◽  
Zebrafish Embryos ◽  
Lateral Plate Mesoderm ◽  
Lateral Plate ◽  
Left Right Asymmetry ◽  
The Right ◽  
Pitx2 Expression

Left-right asymmetry in vertebrates is controlled by activities emanating from the left lateral plate. How these signals get transmitted to the forming organs is not known. A candidate mediator in mouse, frog and zebrafish embryos is the homeobox gene Pitx2. It is asymmetrically expressed in the left lateral plate mesoderm, tubular heart and early gut tube. Localized Pitx2 expression continues when these organs undergo asymmetric looping morphogenesis. Ectopic expression of Xnr1 in the right lateral plate induces Pitx2 transcription in Xenopus. Misexpression of Pitx2 affects situs and morphology of organs. These experiments suggest a role for Pitx2 in promoting looping of the linear heart and gut.

Two distinct endothelial lineages in ontogeny, one of them related to hemopoiesis

Development ◽  
1996 ◽  
Vol 122 (5) ◽  
pp. 1363-1371 ◽  
Author(s):  
L. Pardanaud ◽  
D. Luton ◽  
M. Prigent ◽  
L.M. Bourcheix ◽  
M. Catala ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Body Wall ◽  
The Body ◽  
Paraxial Mesoderm ◽  
Lateral Plate Mesoderm ◽  
Hemopoietic Precursors ◽  
Lateral Plate ◽  
Visceral Organs ◽  
Endothelial Precursors

We have shown previously by means of quail/chick transplantations that external and visceral organs, i.e., somatopleural and splanchnopleural derivatives, acquire their endothelial network through different mechanisms, namely immigration (termed angiogenesis) versus in situ emergence of precursors (or vasculogenesis). We have traced the distribution of QH1-positive cells in chick hosts after replacement of the last somites by quail somites (orthotopic grafts) or lateral plate mesoderm (heterotopic grafts). The results lead to the conclusion that the embryo becomes vascularized by endothelial precursors from two distinct regions, splanchnopleural mesoderm and paraxial mesoderm. The territories respectively vascularized are complementary, precursors from the paraxial mesoderm occupy the body wall and kidney, i.e., they settle along with the other paraxial mesoderm derivatives and colonize the somatopleure. The precursors from the two origins have distinct recognition and potentialities properties: endothelial precursors of paraxial origin are barred from vascularizing visceral organs and from integrating into the floor of the aorta, and are never associated with hemopoiesis; splanchnopleural mesoderm grafted in the place of somites, gives off endothelial cells to body wall and kidney but also visceral organs. It gives rise to hemopoietic precursors in addition to endothelial cells.

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