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 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.

Not Just Inductive: A Critical Mechanical Role for the Endoderm During Heart Tube Assembly

2012 ◽  
Author(s):  
Victor D. Varner ◽  
Larry A. Taber
Keyword(s):  
Close Contact ◽  
Ventral Side ◽  
Lateral Plate Mesoderm ◽  
Heart Tube ◽  
Lateral Plate ◽  
Cardiac Progenitors ◽  
Cardiac Specification ◽  
Tube Assembly ◽  
Heart Fields

The heart is the first functioning organ to form during development. Similar to other organ primordia, the embryonic heart forms as a simple tube — in this case, a straight muscle-wrapped tube situated on the ventral side of the embryo. During gastrulation, the cardiac progenitors reside in the lateral plate mesoderm but maintain close contact with the underlying endoderm. In amniotes, these bilateral heart fields are initially organized as a pair of flat epithelia that move toward the embryonic midline and fuse above the anterior intestinal portal (AIP) to form the heart tube. This medial motion is typically attributed to active mesodermal migration over the underlying endoderm. In this view, the role of the endoderm is two-fold: to serve as a mechanically passive substrate for the crawling mesoderm and to secrete various growth factors necessary for cardiac specification and differentiation.

Hindlimb patterning and mandible development require the Ptx1 gene

Development ◽  
1999 ◽  
Vol 126 (9) ◽  
pp. 1805-1810 ◽  
Author(s):  
C. Lanctot ◽  
A. Moreau ◽  
M. Chamberland ◽  
M.L. Tremblay ◽  
J. Drouin
Keyword(s):  
Gene Knockout ◽  
Proximal Part ◽  
Branchial Arch ◽  
Dorsal Side ◽  
Lateral Plate Mesoderm ◽  
Lateral Plate ◽  
Similar Time ◽  
The Right ◽  
Tetrapod Evolution

The restricted expression of the Ptx1 (Pitx1) gene in the posterior half of the lateral plate mesoderm has suggested that it may play a role in specification of posterior structures, in particular, specification of hindlimb identity. Ptx1 is also expressed in the most anterior ectoderm, the stomodeum, and in the first branchial arch. Ptx1 expression overlaps with that of Ptx2 in stomodeum and in posterior left lateral plate mesoderm. We now show that targeted inactivation of the mouse Ptx1 gene severely impairs hindlimb development: the ilium and knee cartilage are absent and the long bones are underdeveloped. Greater reduction of the right femur size in Ptx1 null mice suggests partial compensation by Ptx2 on the left side. The similarly sized tibia and fibula of mutant hindlimbs may be taken to resemble forelimb bones: however, the mutant limb buds appear to have retained their molecular identity as assessed by forelimb expression of Tbx5 and by hindlimb expression of Tbx4, even though Tbx4 expression is decreased in Ptx1 null mice. The hindlimb defects appear to be, at least partly, due to abnormal chondrogenesis. Since the most affected structures derive from the dorsal side of hindlimb buds, the data suggest that Ptx1 is responsible for patterning of these dorsal structures and that as such it may control development of hindlimb-specific features. Ptx1 inactivation also leads to loss of bones derived from the proximal part of the mandibular mesenchyme. The dual role of Ptx1 revealed by the gene knockout may reflect features of the mammalian jaw and hindlimbs that were acquired at a similar time during tetrapod evolution.

The allocation of epiblast cells to the embryonic heart and other mesodermal lineages: the role of ingression and tissue movement during gastrulation

Development ◽  
1997 ◽  
Vol 124 (9) ◽  
pp. 1631-1642 ◽  
Author(s):  
P.P. Tam ◽  
M. Parameswaran ◽  
S.J. Kinder ◽  
R.P. Weinberger
Keyword(s):  
Cell Fate ◽  
Primitive Streak ◽  
Heart Cells ◽  
Lateral Plate Mesoderm ◽  
Lateral Plate ◽  
Tissue Movement ◽  
Heart Field ◽  
Morphogenetic Event ◽  
Extraembryonic Mesoderm

The cardiogenic potency of cells in the epiblast of the early primitive-streak stage (early PS) embryo was tested by heterotopic transplantation. The results of this study show that cells in the anterior and posterior epiblast of the early PS-stage embryos have similar cardiogenic potency, and that they differentiated to heart cells after they were transplanted directly to the heart field of the late PS embryo. That the epiblast cells can acquire a cardiac fate without any prior act of ingression through the primitive streak or movement within the mesoderm suggests that neither morphogenetic event is critical for the specification of the cardiogenic fate. The mesodermal cells that have recently ingressed through the primitive streak can express a broad cell fate that is characteristic of the pre-ingressed cells in the host when they were returned to the epiblast. However, mesoderm cells that have ingressed through the primitive streak did not contribute to the lateral plate mesoderm after transplantation back to the epiblast, implying that some restriction of lineage potency may have occurred during ingression. Early PS stage epiblast cells that were transplanted to the epiblast of the mid PS host embryos colonised the embryonic mesoderm but not the extraembryonic mesoderm. This departure from the normal cell fate indicates that the allocation of epiblast cells to the mesodermal lineages is dependent on the timing of their recruitment to the primitive streak and the morphogenetic options that are available to the ingressing cells at that instance.

scholarly journals Maternal control of visceral asymmetry evolution in Astyanax cavefish

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Li Ma ◽  
Mandy Ng ◽  
Janet Shi ◽  
Aniket V. Gore ◽  
Daniel Castranova ◽  
...  
Keyword(s):  
Heart Development ◽  
Nodal Signaling ◽  
Lateral Plate Mesoderm ◽  
Visceral Organ ◽  
Maternal Control ◽  
Lateral Plate ◽  
Astyanax Mexicanus ◽  
Evolutionary Changes ◽  
Liver And Pancreas ◽  
Surface Dwelling

AbstractThe direction of visceral organ asymmetry is highly conserved during vertebrate evolution with heart development biased to the left and pancreas and liver development restricted to opposing sides of the midline. Here we show that reversals in visceral organ asymmetry have evolved in Astyanax mexicanus, a teleost species with interfertile surface-dwelling (surface fish) and cave-dwelling (cavefish) forms. Visceral organ asymmetry is conventional in surface fish but some cavefish have evolved reversals in heart, liver, and pancreas development. Corresponding changes in the normally left-sided expression of the Nodal-Pitx2/Lefty signaling system are also present in the cavefish lateral plate mesoderm (LPM). The Nodal antagonists lefty1 (lft1) and lefty2 (lft2), which confine Nodal signaling to the left LPM, are expressed in most surface fish, however, lft2, but not lft1, expression is absent during somitogenesis of most cavefish. Despite this difference, multiple lines of evidence suggested that evolutionary changes in L-R patterning are controlled upstream of Nodal-Pitx2/Lefty signaling. Accordingly, reciprocal hybridization of cavefish and surface fish showed that modifications of heart asymmetry are present in hybrids derived from cavefish mothers but not from surface fish mothers. The results indicate that changes in visceral asymmetry during cavefish evolution are influenced by maternal genetic effects.

scholarly journals Essential roles of zebrafish bmp2a, fgf10, and fgf24 in the specification of the ventral pancreas

2012 ◽  
Vol 23 (5) ◽  
pp. 945-954 ◽  
Author(s):  
François Naye ◽  
Marianne L. Voz ◽  
Nathalie Detry ◽  
Matthias Hammerschmidt ◽  
Bernard Peers ◽  
...  
Keyword(s):  
Fibroblast Growth ◽  
Lateral Plate Mesoderm ◽  
Loss Of Function ◽  
Lateral Plate ◽  
Bmp Pathway ◽  
Ventral Pancreas ◽  
Pancreas Agenesis ◽  
Gut Endoderm ◽  
Hepatic Markers

In vertebrates, pancreas and liver arise from bipotential progenitors located in the embryonic gut endoderm. Bone morphogenic protein (BMP) and fibroblast growth factor (FGF) signaling pathways have been shown to induce hepatic specification while repressing pancreatic fate. Here we show that BMP and FGF factors also play crucial function, at slightly later stages, in the specification of the ventral pancreas. By analyzing the pancreatic markers pdx1, ptf1a, and hlxb9la in different zebrafish models of BMP loss of function, we demonstrate that the BMP pathway is required between 20 and 24 h postfertilization to specify the ventral pancreatic bud. Knockdown experiments show that bmp2a, expressed in the lateral plate mesoderm at these stages, is essential for ventral pancreas specification. Bmp2a action is not restricted to the pancreatic domain and is also required for the proper expression of hepatic markers. By contrast, through the analysis of fgf10−/−; fgf24−/− embryos, we reveal the specific role of these two FGF ligands in the induction of the ventral pancreas and in the repression of the hepatic fate. These mutants display ventral pancreas agenesis and ectopic masses of hepatocytes. Overall, these data highlight the dynamic role of BMP and FGF in the patterning of the hepatopancreatic region.

scholarly journals Opposing RA and FGF signals control proximodistal vertebrate limb development through regulation of Meis genes

Development ◽  
2000 ◽  
Vol 127 (18) ◽  
pp. 3961-3970 ◽  
Author(s):  
N. Mercader ◽  
E. Leonardo ◽  
M.E. Piedra ◽  
C. Martinez-A ◽  
M.A. Ros ◽  
...  
Keyword(s):  
Limb Development ◽  
Fibroblast Growth ◽  
Specific Function ◽  
Lateral Plate Mesoderm ◽  
Lateral Plate ◽  
Vertebrate Limb ◽  
Proximal Determinant ◽  
Vertebrate Limb Development ◽  
Limb Initiation

Vertebrate limbs develop in a temporal proximodistal sequence, with proximal regions specified and generated earlier than distal ones. Whereas considerable information is available on the mechanisms promoting limb growth, those involved in determining the proximodistal identity of limb parts remain largely unknown. We show here that retinoic acid (RA) is an upstream activator of the proximal determinant genes Meis1 and Meis2. RA promotes proximalization of limb cells and endogenous RA signaling is required to maintain the proximal Meis domain in the limb. RA synthesis and signaling range, which initially span the entire lateral plate mesoderm, become restricted to proximal limb domains by the apical ectodermal ridge (AER) activity following limb initiation. We identify fibroblast growth factor (FGF) as the main molecule responsible for this AER activity and propose a model integrating the role of FGF in limb cell proliferation, with a specific function in promoting distalization through inhibition of RA production and signaling.

scholarly journals Primary Cilium Polarity: Morphogenetic Consequences

2018 ◽  
Author(s):  
M. 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.

The Zebrafish Homologue of the Murine Ecotropic Viral Integration Site-1 (. Evi-1) gene Regulates Zebrafish Embryonic Blood Development.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1461-1461
Author(s):  
Martina Konantz ◽  
Martijn H. Brugman ◽  
In-Hyun Park ◽  
George Q. Daley ◽  
Christiane Nuesslein-Volhard ◽  
...  
Keyword(s):  
Stem Cell ◽  
Embryonic Development ◽  
Integration Site ◽  
Myeloid Cells ◽  
Ips Cells ◽  
Viral Integration ◽  
Lateral Plate Mesoderm ◽  
Lateral Plate ◽  
Hematopoietic Development

Abstract Abstract 1461 Poster Board I-484 The ecotropic viral integration site-1 (Evi-1) locus was originally identified as a common site of retroviral integration in murine myeloid tumors and was later shown to be one of the most potent oncogenenes associated with murine and human myeloid leukemia. More recent data suggest involvement of Evi-1 in embryonic hematopoiesis (Goyama et al, Cell Stem Cell 2008; Yuasa et al, EMBO J, 2005), yet the precise role and molecular regulation of Evi-1 during blood development remains poorly understood. The zebrafish model offers powerful tools for genetic and embryonic studies. Here, we study zebrafish embryonic development and human pluripotent stem cells to understand how evi-1 modulates early hematopoietic development. Loss-of-function studies were performed in vivo by injecting Morpholino oligonucleotides in zebrafish zygotes to inhibit evi-1 pre-mRNA splicing. To control for off-target effects, two separate morpholinos were designed and injected. N=100 zebrafish were analysed pro experiment in each group. Inhibition of evi-1 was confirmed by quantitative PCR comparison in morpholino-injected and control embryos. Hematopoietic development was followed in both morphants and wild-type embryos by simple microscopy and in situ hybridizations using known hematopoeitic markers in order to investigate the developmental time-point in which evi-1 regulates blood development. evi-1 morpholino injected zebrafisch embryo showed severely reduced numbers of circulating blood cells, consistent with the phenotype observed in Evi-1−/− mice. Additionally, hemorrhages were observed, suggesting concomittant defects of the endothelial lineage in evi-1 deficient fish. In situ hybridization analysis on 11-12 somite stage embryos revealed strong reduction of myeloid embryonic hematopoiesis (measured by pu.1 expression in the anterior lateral plate mesoderm), while no change was observed in primitive erythroid progenitor cells (monitored by gata1 expression) or overall in blood and endothelial precursors in the posterior lateral plate mesoderm (as monitored by scl expression). Taken together, our studies demonstrate a strong impact of evi-1 on zebrafish blood development, confirming the results from Evi-1−/− mice. As gata1 expression and therefore erythroid precursor cells in the posterior blood islands are unaffected in evi-1 morphants, our results support the hypothesis that the reduction of primitive yolk-sac erythrocytes in mutant mice was caused from hemorrhages from pericardial effusions. Since erythroid and myeloid cells derive from a common precursor, but gata1 expression was unaffected in knock-down embryos, we anticipate that evi-1 plays a specific role in the myeloid lineage, as shown by abolished pu.1 expression in the anterior LPM. evi-1 therefore probably affects differentiation, survival or proliferation of myeloid cells. Previous reports in adult hematopoietic cells show that evi-1 can interact with both gata1 and pu.1. However, our data suggest that this is not the case during embryonic development, since gata1 expression remained unaltered in morpholino-injected embryos. Furthermore, data in mice suggest that Evi-1 may modulate embryonic hematopoiesis by affecting hematopoietic stem cell proliferation through regulation of Gata2. Currently ongoing experiments in our laboratories focus on characterization of genetic interactions between evi-1, gata2 and pu.1 during zebrafish blood development. Amongst other, gata2 and respectively pu.1 mRNA are co-injected in evi-1 morphants to analyse whether they can rescue the blood phenotype. Moreover, selected findings in zebrafish embryonic development will be verified in the human using using in vitro differentiating human induced pluripotent stem (iPS) cells. First expression data generated by real-time PCR analysis showed differential expression of EVI-1 in embryoid bodies generated from human iPS cells, confirming our hypothesis that EVI-1 has specific effects during human blood development. Disclosures No relevant conflicts of interest to declare.

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.

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