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

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.

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

eLife ◽

10.7554/elife.29106 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 5

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.

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Somite Compartments in Amphioxus and Its Implications on the Evolution of the Vertebrate Skeletal Tissues

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.607057 ◽

2021 ◽

Vol 9 ◽

Author(s):

Luok Wen Yong ◽

Tsai-Ming Lu ◽

Che-Huang Tung ◽

Ruei-Jen Chiou ◽

Kun-Lung Li ◽

...

Keyword(s):

Neural Tube ◽

Developmental Process ◽

Lateral Wall ◽

Bmp Signaling ◽

Lateral Plate Mesoderm ◽

Evolutionary Novelty ◽

Lateral Plate ◽

Collagenous Matrix ◽

Previous Hypothesis ◽

Collagen Genes

Mineralized skeletal tissues of vertebrates are an evolutionary novelty within the chordate lineage. While the progenitor cells that contribute to vertebrate skeletal tissues are known to have two embryonic origins, the mesoderm and neural crest, the evolutionary origin of their developmental process remains unclear. Using cephalochordate amphioxus as our model, we found that cells at the lateral wall of the amphioxus somite express SPARC (a crucial gene for tissue mineralization) and various collagen genes. During development, some of these cells expand medially to surround the axial structures, including the neural tube, notochord and gut, while others expand laterally and ventrally to underlie the epidermis. Eventually these cell populations are found closely associated with the collagenous matrix around the neural tube, notochord, and dorsal aorta, and also with the dense collagen sheets underneath the epidermis. Using known genetic markers for distinct vertebrate somite compartments, we showed that the lateral wall of amphioxus somite likely corresponds to the vertebrate dermomyotome and lateral plate mesoderm. Furthermore, we demonstrated a conserved role for BMP signaling pathway in somite patterning of both amphioxus and vertebrates. These results suggest that compartmentalized somites and their contribution to primitive skeletal tissues are ancient traits that date back to the chordate common ancestor. The finding of SPARC-expressing skeletal scaffold in amphioxus further supports previous hypothesis regarding SPARC gene family expansion in the elaboration of the vertebrate mineralized skeleton.

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

Development ◽

10.1242/dev.129.14.3431 ◽

2002 ◽

Vol 129 (14) ◽

pp. 3431-3440 ◽

Cited By ~ 2

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.

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Hyperglycemia impairs left–right axis formation and thereby disturbs heart morphogenesis in mouse embryos

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1504529112 ◽

2015 ◽

Vol 112 (38) ◽

pp. E5300-E5307 ◽

Cited By ~ 13

Author(s):

Masahiro Hachisuga ◽

Shinya Oki ◽

Keiko Kitajima ◽

Satomi Ikuta ◽

Tomoyuki Sumi ◽

...

Keyword(s):

Notch Signaling ◽

High Glucose ◽

Cardiac Development ◽

Heart Defects ◽

Mouse Embryos ◽

Axis Formation ◽

Lateral Plate Mesoderm ◽

Lateral Plate ◽

Heart Morphogenesis ◽

Insight Into

Congenital heart defects with heterotaxia are associated with pregestational diabetes mellitus. To provide insight into the mechanisms underlying such diabetes-related heart defects, we examined the effects of high-glucose concentrations on formation of the left–right axis in mouse embryos. Expression ofPitx2, which plays a key role in left–right asymmetric morphogenesis and cardiac development, was lost in the left lateral plate mesoderm of embryos of diabetic dams. Embryos exposed to high-glucose concentrations in culture also failed to expressNodalandPitx2in the left lateral plate mesoderm. The distribution of phosphorylated Smad2 revealed that Nodal activity in the node was attenuated, accounting for the failure of left–right axis formation. Consistent with this notion, Notch signal-dependent expression of Nodal-related genes in the node was also down-regulated in association with a reduced level of Notch signaling, suggesting that high-glucose concentrations impede Notch signaling and thereby hinder establishment of the left–right axis required for heart morphogenesis.

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The origin and movements of the hepatogenic cells in the chick embryo as determined by radioautographic mapping

Development ◽

10.1242/dev.25.1.97 ◽

1971 ◽

Vol 25 (1) ◽

pp. 97-113

Author(s):

Glenn C. Rosenquist

Keyword(s):

Chick Embryo ◽

Developmental Stage ◽

Primitive Streak ◽

Limb Bud ◽

Chick Embryos ◽

Lateral Plate Mesoderm ◽

Lateral Plate ◽

Somite Stage ◽

Definition Of ◽

Exact Definition

The origin of the prehepatic cells was determined by tracing the movements of [3H]thymidine-labelled grafts excised from medium-streak to 4-somite stage chick embryos and transplanted to the epiblast, streak and endoderm-mesoderm layer of similarly staged recipient embryos. Although exact definition of prehepatic areas was not possible because of the small number of grafts placed at each developmental stage, the study showed in general that at the medium-streak stage, the prehepatic endoderm cells are in the anterior third of the primitive streak; they shortly begin to migrate anteriorly and laterally into the endoderm layer ventral to the precardiac areas of mesoderm. They are in the yolk-sac endoderm at the 2–4-somite stage, and by the 15–17-somite stage are clustered at the anterior intestinal portal. At the 26-somite to early limb-bud stages, the anterior and posterior liver diverticula have formed from these endoderm cells, and some of the branches of the diverticula may have reached the prehepatic mesenchyme, where the two tissues have begun to form cords and sinuses. At the medium-streak stage, the prehepatic mesoderm is located slightly more than halfway from the anterior to the posterior end of the primitive streak. From this position it migrates anteriorly and laterally into the lateral plate mesoderm, and from the head-process to the 2–4-somite stage it is situated posterior to the prehepatic endoderm and posterior and lateral to the heart-forming portion of the splanchnic layer. By the 15–17-somite stage the prehepatic mesoderm has reached a position in the splanchnic layer of mesoderm which forms the dorsolateral wall of the sinus venosus. By the 26-somite to early limb-bud stage the hepatic diverticula have joined with the hepatic mesenchyme to form the rudimentary cords and sinuses of the liver.

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SPC4/PACE4 regulates a TGFβ signaling network during axis formation

Genes & Development ◽

10.1101/gad.14.9.1146 ◽

2000 ◽

Vol 14 (9) ◽

pp. 1146-1155 ◽

Cited By ~ 2

Author(s):

Daniel B. Constam ◽

Elizabeth J. Robertson

Keyword(s):

Gene Expression Analysis ◽

Bmp Signaling ◽

Genetic Interactions ◽

Axis Formation ◽

Tgfβ Signaling ◽

Craniofacial Malformations ◽

Lateral Plate ◽

Early Mouse Embryo ◽

Situs Ambiguus ◽

Early Mouse

In vertebrates, specification of anteroposterior (A/P) and left–right (L/R) axes depends on TGFβ-related signals, including Nodal, Lefty, and BMPs. Endoproteolytic maturation of these proteins is probably mediated by the proprotein convertase SPC1/Furin. In addition, precursor processing may be regulated by related activities such as SPC4 (also known as PACE4). Here, we show that a proportion of embryos lacking SPC4 develop situs ambiguus combined with left pulmonary isomerism or complex craniofacial malformations including cyclopia, or both. Gene expression analysis during early somite stages indicates that spc4 is genetically upstream of nodal, pitx2, lefty1, and lefty2 and perhaps maintains the balance between Nodal and BMP signaling in the lateral plate that is critical for L/R axis formation. Furthermore, genetic interactions betweennodal and spc4, together with our analysis of chimeric embryos, strongly suggest that during A/P axis formation, SPC4 acts primarily in the foregut. These findings establish an important role for SPC4 in patterning the early mouse embryo.

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