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.

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.

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.

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.

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.

Zic3 is involved in the left-right specification of the Xenopus embryo

Development ◽  
2000 ◽  
Vol 127 (22) ◽  
pp. 4787-4795 ◽  
Author(s):  
T. Kitaguchi ◽  
T. Nagai ◽  
K. Nakata ◽  
J. Aruga ◽  
K. Mikoshiba
Keyword(s):  
Molecular Basis ◽  
Xenopus Embryo ◽  
Zinc Finger Domain ◽  
Lateral Plate Mesoderm ◽  
Vertebrate Development ◽  
Gastrula Stage ◽  
Lateral Plate ◽  
The Right ◽  
Early Gastrula ◽  
Pitx2 Expression

Establishment of left-right (L-R) asymmetry is fundamental to vertebrate development. Several genes involved in L-R asymmetry have been described. In the Xenopus embryo, Vg1/activin signals are implicated upstream of asymmetric nodal related 1 (Xnr1) and Pitx2 expression in L-R patterning. We report here that Zic3 carries the left-sided signal from the initial activin-like signal to determinative factors such as Pitx2. Overexpression of Zic3 on the right side of the embryo altered the orientation of heart and gut looping, concomitant with disturbed laterality of expression of Xnr1 and Pitx2, both of which are normally expressed in the left lateral plate mesoderm. The results indicate that Zic3 participates in the left-sided signaling upstream of Xnr1 and Pitx2. At early gastrula, Zic3 was expressed not only in presumptive neuroectoderm but also in mesoderm. Correspondingly, overexpression of Zic3 was effective in the L-R specification at the early gastrula stage, as revealed by a hormone-inducible Zic3 construct. The Zic3 expression in the mesoderm is induced by activin (beta) or Vg1, which are also involved in the left-sided signal in L-R specification. These findings suggest that an activin-like signal is a potent upstream activator of Zic3 that establishes the L-R axis. Furthermore, overexpression of the zinc-finger domain of Zic3 on the right side is sufficient to disturb the L-R axis, while overexpression of the N-terminal domain on the left side affects the laterality. These results suggest that Zic3 has at least two functionally important domains that play different roles and provide a molecular basis for human heterotaxy, which is an L-R pattern anomaly caused by a mutation in human ZIC3.

scholarly journals Persistent Ventricle Partitioning in the Adult Zebrafish Heart

2021 ◽  
Vol 8 (4) ◽  
pp. 41
Author(s):  
Catherine Pfefferli ◽  
Hannah R. Moran ◽  
Anastasia Felker ◽  
Christian Mosimann ◽  
Anna Jaźwińska
Keyword(s):  
Lateral Plate Mesoderm ◽  
Adult Zebrafish ◽  
Lateral Plate ◽  
Second Heart Field ◽  
Heart Field ◽  
Left And Right ◽  
First Heart Field ◽  
The Right ◽  
Physical Boundary ◽  
Zebrafish Heart

The vertebrate heart integrates cells from the early-differentiating first heart field (FHF) and the later-differentiating second heart field (SHF), both emerging from the lateral plate mesoderm. In mammals, this process forms the basis for the development of the left and right ventricle chambers and subsequent chamber septation. The single ventricle-forming zebrafish heart also integrates FHF and SHF lineages during embryogenesis, yet the contributions of these two myocardial lineages to the adult zebrafish heart remain incompletely understood. Here, we characterize the myocardial labeling of FHF descendants in both the developing and adult zebrafish ventricle. Expanding previous findings, late gastrulation-stage labeling using drl-driven CreERT2 recombinase with a myocardium-specific, myl7-controlled, loxP reporter results in the predominant labeling of FHF-derived outer curvature and the right side of the embryonic ventricle. Raised to adulthood, such lineage-labeled hearts retain broad areas of FHF cardiomyocytes in a region of the ventricle that is positioned at the opposite side to the atrium and encompasses the apex. Our data add to the increasing evidence for a persisting cell-based compartmentalization of the adult zebrafish ventricle even in the absence of any physical boundary.

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.

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.

Dermomyotomal origin of the ribs as revealed by extirpation and transplantation experiments in chick and quail embryos

Development ◽  
1998 ◽  
Vol 125 (17) ◽  
pp. 3437-3443 ◽  
Author(s):  
N. Kato ◽  
H. Aoyama
Keyword(s):  
Distal Part ◽  
Proximal Part ◽  
Axial Skeleton ◽  
Middle Part ◽  
Medial Part ◽  
Lateral Plate ◽  
Intercostal Muscles ◽  
Transplantation Experiments ◽  
Chick And Quail Embryos

To elucidate role of the dermomyotome in the formation of the axial skeleton, we performed extirpation and transplantation experiments on the dermomyotomes in chick and quail embryos. When the thoracic dermomyotomes of chick embryos were removed, the intercostal muscles and the distal ribs were deficient, while the proximal ribs were more or less normal. Quail tissues including the dermomyotome, the ectoderm and the medial edge of lateral plate, were transplanted to replace chick dermomyotomes. In these chimeras, the ribs, which would be deficient without the back-transplantation, were recovered. The cells of the recovered part of the ribs as well as the intercostal muscles were derived from the quail transplants. These findings suggest that the distal rib originated from the dermomyotomes and not the sclerotome as previously believed. To localize the origin of the distal rib further, we removed restricted regions of the dermomyotomes along the mediolateral and the rostrocaudal axis. The more lateral the part of the dermomyotomes that we removed, the more distal the part of the ribs affected. On the contrary, when the rostral and caudal edges of the dermomyotomes were removed, only the vertebral ribs showed extensive deficiencies while removal of the middle part between the edges caused less deficiency. The sternal ribs were not deficient in either case, but were extensively affected when the entire lateral edge of dermomyotomes was included in the region removed. We conclude that the lateral edges of the dermomyotomes are the primordia of the sternal ribs, and the rostral and/or caudal edges of the medial part of dermomyotomes are the primordia of the distal part and not of the proximal part of the vertebral ribs.

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