Otx2 is required for visceral endoderm movement and for the restriction of posterior signals in the epiblast of the mouse embryo

Development ◽  
2001 ◽  
Vol 128 (5) ◽  
pp. 753-765 ◽  
Author(s):  
A. Perea-Gomez ◽  
K.A. Lawson ◽  
M. Rhinn ◽  
L. Zakin ◽  
P. Brulet ◽  
...  
Keyword(s):  
Essential Role ◽  
Homeobox Gene ◽  
Primitive Streak ◽  
Lineage Tracing ◽  
Secreted Proteins ◽  
Visceral Endoderm ◽  
Cellular Mechanisms ◽  
Cell Fates ◽  
Marker Studies ◽  
Anterior Visceral Endoderm

Genetic and embryological experiments have demonstrated an essential role for the visceral endoderm in the formation of the forebrain; however, the precise molecular and cellular mechanisms of this requirement are poorly understood. We have performed lineage tracing in combination with molecular marker studies to follow morphogenetic movements and cell fates before and during gastrulation in embryos mutant for the homeobox gene Otx2. Our results show, first, that Otx2 is not required for proliferation of the visceral endoderm, but is essential for anteriorly directed morphogenetic movement. Second, molecules that are normally expressed in the anterior visceral endoderm, such as Lefty1 and Mdkk1, are not expressed in Otx2 mutants. These secreted proteins have been reported to antagonise, respectively, the activities of Nodal and Wnt signals, which have a role in regulating primitive streak formation. The visceral endoderm defects of the Otx2 mutants are associated with abnormal expression of primitive streak markers in the epiblast, suggesting that anterior epiblast cells acquire primitive streak characteristics. Taken together, our data support a model whereby Otx2 functions in the anterior visceral endoderm to influence the ability of the adjacent epiblast cells to differentiate into anterior neurectoderm, indirectly, by preventing them from coming under the influence of posterior signals that regulate primitive streak formation.

Head induction in the chick by primitive endoderm of mammalian, but not avian origin

Development ◽  
1999 ◽  
Vol 126 (4) ◽  
pp. 815-825 ◽  
Author(s):  
H. Knoetgen ◽  
C. Viebahn ◽  
M. Kessel
Keyword(s):  
Lower Layer ◽  
Homeobox Gene ◽  
Primitive Streak ◽  
Neural Plate ◽  
Visceral Endoderm ◽  
Avian Origin ◽  
Bmp Antagonist ◽  
Rabbit Embryos ◽  
Inductive Potential ◽  
Anterior Visceral Endoderm

Different types of endoderm, including primitive, definitive and mesendoderm, play a role in the induction and patterning of the vertebrate head. We have studied the formation of the anterior neural plate in chick embryos using the homeobox gene GANF as a marker. GANF is first expressed after mesendoderm ingression from Hensen's node. We found that, after transplantation, neither the avian hypoblast nor the anterior definitive endoderm is capable of GANF induction, whereas the mesendoderm (young head process, prechordal plate) exhibits a strong inductive potential. GANF induction cannot be separated from the formation of a proper neural plate, which requires an intact lower layer and the presence of the prechordal mesendoderm. It is inhibited by BMP4 and promoted by the presence of the BMP antagonist Noggin. In order to investigate the inductive potential of the mammalian visceral endoderm, we used rabbit embryos which, in contrast to mouse embryos, allow the morphological recognition of the prospective anterior pole in the living, pre-primitive-streak embryo. The anterior visceral endoderm from such rabbit embryos induced neuralization and independent, ectopic GANF expression domains in the area pellucida or the area opaca of chick hosts. Thus, the signals for head induction reside in the anterior visceral endoderm of mammals whereas, in birds and amphibia, they reside in the prechordal mesendoderm, indicating a heterochronic shift of the head inductive capacity during the evolution of mammalia.

scholarly journals Correct Patterning of the Primitive Streak Requires the Anterior Visceral Endoderm

PLoS ONE ◽  
2011 ◽  
Vol 6 (3) ◽  
pp. e17620 ◽  
Author(s):  
Daniel W. Stuckey ◽  
Aida Di Gregorio ◽  
Melanie Clements ◽  
Tristan A. Rodriguez
Keyword(s):  
Primitive Streak ◽  
Visceral Endoderm ◽  
Anterior Visceral Endoderm

HNF3beta and Lim1 interact in the visceral endoderm to regulate primitive streak formation and anterior-posterior polarity in the mouse embryo

Development ◽  
1999 ◽  
Vol 126 (20) ◽  
pp. 4499-4511 ◽  
Author(s):  
A. Perea-Gomez ◽  
W. Shawlot ◽  
H. Sasaki ◽  
R.R. Behringer ◽  
S. Ang
Keyword(s):  
Mouse Embryo ◽  
Primitive Streak ◽  
Axis Formation ◽  
Visceral Endoderm ◽  
Primary Defect ◽  
Homozygous Mutant ◽  
Early Mouse ◽  
Mesoderm Patterning ◽  
Anterior Posterior ◽  
Anterior Visceral Endoderm

Recent embryological and genetic experiments have suggested that the anterior visceral endoderm and the anterior primitive streak of the early mouse gastrula function as head- and trunk-organising centers, respectively. Here, we report that HNF3beta and Lim1 are coexpressed in both organising centers suggesting synergistic roles of these genes in regulating organiser functions and hence axis development in the mouse embryo. To investigate this possibility, we generated compound HNF3beta and Lim1 mutant embryos. An enlarged primitive streak and a lack of axis formation were observed in HNF3beta (−)(/)(−);Lim1(−)(/)(−), but not in single homozygous mutant embryos. Chimera experiments indicate that the primary defect in these double homozygous mutants is due to loss of activity of HNF3beta and Lim1 in the visceral endoderm. Altogether, these data provide evidence that these genes function synergistically to regulate organiser activity of the anterior visceral endoderm. Moreover, HNF3beta (−)(/)(−);Lim1(−)(/)(−) mutant embryos also exhibit defects in mesoderm patterning that are likely due to lack of specification of anterior primitive streak cells.

Lim1 is required in both primitive streak-derived tissues and visceral endoderm for head formation in the mouse

Development ◽  
1999 ◽  
Vol 126 (22) ◽  
pp. 4925-4932 ◽  
Author(s):  
W. Shawlot ◽  
M. Wakamiya ◽  
K.M. Kwan ◽  
A. Kania ◽  
T.M. Jessell ◽  
...  
Keyword(s):  
Marker Gene ◽  
Embryonic Stem ◽  
Homeobox Gene ◽  
Primitive Streak ◽  
Mouse Embryos ◽  
Chimeric Mouse ◽  
Visceral Endoderm ◽  
Wild Type ◽  
Targeted Mutation ◽  
Head Formation

Lim1 is a homeobox gene expressed in the extraembryonic anterior visceral endoderm and in primitive streak-derived tissues of early mouse embryos. Mice homozygous for a targeted mutation of Lim1 lack head structures anterior to rhombomere 3 in the hindbrain. To determine in which tissues Lim1 is required for head formation and its mode of action, we have generated chimeric mouse embryos and performed tissue layer recombination explant assays. In chimeric embryos in which the visceral endoderm was composed of predominantly wild-type cells, we found that Lim1(−)(/)(−) cells were able to contribute to the anterior mesendoderm of embryonic day 7.5 chimeric embryos but that embryonic day 9.5 chimeric embryos displayed a range of head defects. In addition, early somite stage chimeras generated by injecting Lim1(−)(/)(−) embryonic stem cells into wild-type tetraploid blastocysts lacked forebrain and midbrain neural tissue. Furthermore, in explant recombination assays, anterior mesendoderm from Lim1(−)(/)(−) embryos was unable to maintain the expression of the anterior neural marker gene Otx2 in wild-type ectoderm. In complementary experiments, embryonic day 9.5 chimeric embryos in which the visceral endoderm was composed of predominantly Lim1(−)(/)(−) cells and the embryo proper of largely wild-type cells, also phenocopied the Lim1(−)(/)(−) headless phenotype. These results indicate that Lim1 is required in both primitive streak-derived tissues and visceral endoderm for head formation and that its inactivation in these tissues produces cell non-autonomous defects. We discuss a double assurance model in which Lim1 regulates sequential signaling events required for head formation in the mouse.

scholarly journals Characterisation of the transcriptional dynamics underpinning the function, fate, and migration of the mouse Anterior Visceral Endoderm

2021 ◽  
Author(s):  
Shifaan Thowfeequ ◽  
Jonathan Fiorentino ◽  
Di Hu ◽  
Maria Solovey ◽  
Sharon Ruane ◽  
...  
Keyword(s):  
Primitive Streak ◽  
Pharmacological Intervention ◽  
Visceral Endoderm ◽  
Migratory Behaviour ◽  
Tight Coupling ◽  
Transient Nature ◽  
Transcriptional Dynamics ◽  
And Migration ◽  
And Function ◽  
Anterior Visceral Endoderm

During early post-implantation development of the mouse embryo, the Anterior Visceral Endoderm (AVE) differs from surrounding visceral endoderm (VE) in its migratory behaviour and ability to restrict primitive streak formation to the opposite side of the egg cylinder. In order to characterise the molecular basis for the unique properties of the AVE, we combined single-cell RNA-sequencing of the VE prior to and during AVE migration, with high-resolution imaging, short-term lineage labelling, phosphoproteomics and pharmacological intervention. This revealed the transient nature of the AVE, the emergence of heterogeneities in AVE transcriptional states relative to position of cells, and its prominence in establishing gene expression asymmetries within the spatial constraints of the embryo. We identified a previously unknown requirement of Ephrin- and Semaphorin-signalling for AVE migration. These findings point to a tight coupling of transcriptional state and position in the AVE and reveal molecular heterogeneities underpinning its migratory behaviour and function.

Anterior patterning by synergistic activity of the early gastrula organizer and the anterior germ layer tissues of the mouse embryo

Development ◽  
1999 ◽  
Vol 126 (22) ◽  
pp. 5171-5179 ◽  
Author(s):  
P.P. Tam ◽  
K.A. Steiner
Keyword(s):  
Primitive Streak ◽  
Germ Layer ◽  
Synergistic Activity ◽  
Visceral Endoderm ◽  
Neural Genes ◽  
Anterior Patterning ◽  
Host Embryo ◽  
Early Gastrula ◽  
Host Tissues ◽  
Anterior Visceral Endoderm

Fragments of the germ layer tissues isolated from the early-primitive-streak (early-streak) stage mouse embryos were tested for axis induction activity by transplantation to late-gastrula (late-streak to early-bud) stage host embryos. The posterior epiblast fragment that contains the early gastrula organizer was able to recruit the host tissues to form an ectopic axis. However, the most anterior neural gene that was expressed in the ectopic axis was Krox20 that marks parts of the hindbrain, but markers of the mid- and forebrain (Otx2 and En1) were not expressed. Anterior visceral endoderm or the anterior epiblast alone did not induce any ectopic neural tissue. However, when these two anterior germ layer tissues were transplanted together, they can induce the formation of ectopic host-derived neural tissues but these tissues rarely expressed anterior neural genes and did not show any organization of an ectopic axis. Therefore, although the anterior endoderm and epiblast together may display some inductive activity, they do not act like a classical organizer. Induction of the anterior neural genes in the ectopic axis was achieved only when a combination of the posterior epiblast fragment, anterior visceral endoderm and the anterior epiblast was transplanted to the host embryo. The formation of anterior neural structures therefore requires the synergistic interaction of the early gastrula organizer and anterior germ layer tissues.

Misexpression of chick Vg1 in the marginal zone induces primitive streak formation

Development ◽  
1997 ◽  
Vol 124 (24) ◽  
pp. 5127-5138 ◽  
Author(s):  
S.B. Shah ◽  
I. Skromne ◽  
C.R. Hume ◽  
D.S. Kessler ◽  
K.J. Lee ◽  
...  
Keyword(s):  
Marginal Zone ◽  
Ectopic Expression ◽  
Primitive Streak ◽  
Axis Formation ◽  
Mesoderm Induction ◽  
Cell Fates ◽  
Signalling Molecules ◽  
Posterior Area ◽  
Area Pellucida

In the chick embryo, the primitive streak is the first axial structure to develop. The initiation of primitive streak formation in the posterior area pellucida is influenced by the adjacent posterior marginal zone (PMZ). We show here that chick Vg1 (cVg1), a member of the TGFbeta family of signalling molecules whose homolog in Xenopus is implicated in mesoderm induction, is expressed in the PMZ of prestreak embryos. Ectopic expression of cVg1 protein in the marginal zone chick blastoderms directs the formation of a secondary primitive streak, which subsequently develops into an ectopic embryo. We have used cell marking techniques to show that cells that contribute to the ectopic primitive streak change fate, acquiring two distinct properties of primitive streak cells, defined by gene expression and cell movements. Furthermore, naive epiblast explants exposed to cVg1 protein in vitro acquire axial mesodermal properties. Together, these results show that cVg1 can mediate ectopic axis formation in the chick by inducing new cell fates and they permit the analysis of distinct events that occur during primitive streak formation.

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