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

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.

Download Full-text

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

eLife ◽

10.7554/elife.28635 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 25

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.

Download Full-text

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

ASME 2012 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2012-80621 ◽

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.

Download Full-text

The forkhead transcription factor Foxf1 is required for differentiation of extra-embryonic and lateral plate mesoderm

Development ◽

10.1242/dev.128.2.155 ◽

2001 ◽

Vol 128 (2) ◽

pp. 155-166 ◽

Cited By ~ 10

Author(s):

M. Mahlapuu ◽

M. Ormestad ◽

S. Enerback ◽

P. Carlsson

Keyword(s):

Transcription Factor ◽

Cell Adhesion ◽

Posterior Part ◽

Homeobox Gene ◽

Primitive Streak ◽

Yolk Sac ◽

Lateral Plate Mesoderm ◽

Forkhead Transcription Factor ◽

Lateral Plate ◽

Adhesion Properties

The murine Foxf1 gene encodes a forkhead transcription factor expressed in extra-embryonic and lateral plate mesoderm and later in splanchnic mesenchyme surrounding the gut and its derivatives. We have disrupted Foxf1 and show that mutant embryos die at midgestation due to defects in mesodermal differentiation and cell adhesion. The embryos do not turn and become deformed by the constraints of a small, inflexible amnion. Extra-embryonic structures exhibit a number of differentiation defects: no vasculogenesis occurs in yolk sac or allantois; chorioallantoic fusion fails; the amnion does not expand with the growth of the embryo, but misexpresses vascular and hematopoietic markers. Separation of the bulk of yolk sac mesoderm from the endodermal layer and adherence between mesoderm of yolk sac and amnion, indicate altered cell adhesion properties and enhanced intramesodermal cohesion. A possible cause of this is misexpression of the cell-adhesion protein VCAM1 in Foxf1-deficient extra-embryonic mesoderm, which leads to co-expression of VCAM with its receptor, alpha(4)-integrin. The expression level of Bmp4 is decreased in the posterior part of the embryo proper. Consistent with this, mesodermal proliferation in the primitive streak is reduced and somite formation is retarded. Expression of Foxf1 and the homeobox gene Irx3 defines the splanchnic and somatic mesodermal layers, respectively. In Foxf1-deficient embryos incomplete separation of splanchnic and somatic mesoderm is accompanied by misexpression of Irx3 in the splanchnopleure, which implicates Foxf1 as a repressor of Irx3 and as a factor involved in coelom formation.

Download Full-text

Hindlimb patterning and mandible development require the Ptx1 gene

Development ◽

10.1242/dev.126.9.1805 ◽

1999 ◽

Vol 126 (9) ◽

pp. 1805-1810 ◽

Cited By ~ 6

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.

Download Full-text

Cre/lox-controlled spatio-temporal perturbation of FGF signaling in zebrafish

10.1101/302174 ◽

2018 ◽

Cited By ~ 2

Author(s):

Lucia Kirchgeorg ◽

Anastasia Felker ◽

Elena Chiavacci ◽

Christian Mosimann

Keyword(s):

Cell Fate ◽

Dominant Negative ◽

Specific Cell ◽

Lateral Plate Mesoderm ◽

Fgf Signaling ◽

Pectoral Fin ◽

Lateral Plate ◽

Developmental Processes ◽

Spatio Temporal ◽

Temporal Perturbation

Fibroblast Growth Factor (FGF) signaling guides multiple developmental processes including body axis formation and specific cell fate patterning. In zebrafish, genetic mutants and chemical perturbations affecting FGF signaling have uncovered key developmental processes; however, these approaches cause embryo-wide FGF signaling perturbations, rendering assessment of cell-autonomous versus non-autonomous requirements for FGF signaling in individual processes difficult. Here, we created the novel transgenic line fgfr1-dn-cargo, encoding dominant-negative Fgfr1 with fluorescent tag under combined Cre/lox and heatshock control to provide spatio-temporal perturbation of FGF signaling. Validating efficient perturbation of FGF signaling by fgfr1-dn-cargo primed with ubiquitous CreERT2, we established that primed, heatshock-induced fgfr1-dn-cargo behaves akin to pulsed treatment with the FGFR inhibitor SU5402. Priming fgfr1-dn-cargo with CreERT2 in the lateral plate mesoderm, we observed selective cardiac and pectoral fin phenotypes without drastic impact on overall embryo patterning. Harnessing lateral plate mesoderm-specific FGF inhibition, we recapitulated the cell-autonomous and temporal requirement for FGF signaling in pectoral fin outgrow, as previously hypothesized from pan-embryonic FGF inhibition. Altogether, our results establish fgfr1-dn-cargo as a genetic tool to define the spatio-temporal requirements for FGF signaling in zebrafish.

Download Full-text

Persistent Ventricle Partitioning in the Adult Zebrafish Heart

Journal of Cardiovascular Development and Disease ◽

10.3390/jcdd8040041 ◽

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.

Download Full-text

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

Molecular Biology of the Cell ◽

10.1091/mbc.e11-08-0664 ◽

2012 ◽

Vol 23 (5) ◽

pp. 945-954 ◽

Cited By ~ 17

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.

Download Full-text

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

Development ◽

10.1242/dev.127.18.3961 ◽

2000 ◽

Vol 127 (18) ◽

pp. 3961-3970 ◽

Cited By ~ 15

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.

Download Full-text