The role of Pten in anterior–posterior (AP) axis formation in the mouse embryo

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.

Download Full-text

Control of early anterior-posterior patterning in the mouse embryo by TGF-β signalling

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2003.1332 ◽

2003 ◽

Vol 358 (1436) ◽

pp. 1351-1358 ◽

Cited By ~ 40

Author(s):

Elizabeth J. Robertson ◽

Dominic P. Norris ◽

Jane Brennan ◽

Elizabeth K. Bikoff

Keyword(s):

Mouse Embryo ◽

Transforming Growth Factor ◽

Organizer Region ◽

Primitive Streak ◽

Transforming Growth Factor Β ◽

Axis Formation ◽

Posterior Side ◽

Molecular Pattern ◽

Discrete Population ◽

Anterior Posterior

Prior to gastrulation the mouse embryo exists as a symmetrical cylinder consisting of three tissue layers. Positioning of the future anterior–posterior axis of the embryo occurs through coordinated cell movements that rotate a pre–existing proximal–distal (P–D) axis. Overt axis formation becomes evident when a discrete population of proximal epiblast cells become induced to form mesoderm, initiating primitive streak formation and marking the posterior side of the embryo. Over the next 12–24 h the primitive streak gradually elongates along the posterior side of the epiblast to reach the distal tip. The most anterior streak cells comprise the ‘organizer’ region and include the precursors of the so–called ‘axial mesendoderm’, namely the anterior definitive endoderm and prechordal plate mesoderm, as well as those cells that give rise to the morphologically patent node. Signalling pathways controlled by the transforming growth factor–β ligand nodal are involved in orchestrating the process of axis formation. Embryos lacking nodal activity arrest development before gastrulation, reflecting an essential role for nodal in establishing P–D polarity by generating and maintaining the molecular pattern within the epiblast, extraembryonic ectoderm and the visceral endoderm. Using a genetic strategy to manipulate temporal and spatial domains of nodal expression reveals that the nodal pathway is also instrumental in controlling both the morphogenetic movements required for orientation of the final axis and for specification of the axial mesendoderm progenitors.

Download Full-text

Oocyte determination and the origin of polarity in Drosophila: the role of the spindle genes

Development ◽

10.1242/dev.124.24.4927 ◽

1997 ◽

Vol 124 (24) ◽

pp. 4927-4937 ◽

Cited By ~ 20

Author(s):

A. Gonzalez-Reyes ◽

H. Elliott ◽

D. St Johnston

Keyword(s):

Symmetry Breaking ◽

Germinal Vesicle ◽

Follicle Cells ◽

Axis Formation ◽

Main Body ◽

Nurse Cells ◽

Egg Chambers ◽

Anterior Posterior ◽

Oocyte Selection

The two main body axes in Drosophila become polarised as a result of a series of symmetry-breaking steps during oogenesis. Two of the sixteen germline cells in each egg chamber develop as pro-oocytes, and the first asymmetry arises when one of these cells is selected to become the oocyte. Anterior-posterior polarity originates when the oocyte then comes to lie posterior to the nurse cells and signals through the Gurken/Egfr pathway to induce the adjacent follicle cells to adopt a posterior fate. This directs the movement of the germinal vesicle and associated gurken mRNA from the posterior to an anterior corner of the oocyte, where Gurken protein signals for a second time to induce the dorsal follicle cells, thereby polarising the dorsal-ventral axis. Here we describe a group of five genes, the spindle loci, which are required for each of these polarising events. spindle mutants inhibit the induction of both the posterior and dorsal follicle cells by disrupting the localisation and translation of gurken mRNA. Moreover, the oocyte often fails to reach the posterior of mutant egg chambers and differentiates abnormally. Finally, double mutants cause both pro-oocytes to develop as oocytes, by delaying the choice between these two cells. Thus, these mutants reveal a novel link between oocyte selection, oocyte positioning and axis formation in Drosophila, leading us to propose that the spindle genes act in a process that is common to several of these events.

Download Full-text

Sall4 isoforms act during proximal-distal and anterior-posterior axis formation in the mouse embryo

genesis ◽

10.1002/dvg.20421 ◽

2008 ◽

Vol 46 (9) ◽

pp. 463-477 ◽

Cited By ~ 17

Author(s):

Nikolas Uez ◽

Heiko Lickert ◽

Jürgen Kohlhase ◽

Martin Hrabe de Angelis ◽

Ralf Kühn ◽

...

Keyword(s):

Mouse Embryo ◽

Axis Formation ◽

Anterior Posterior ◽

Anterior Posterior Axis

Download Full-text

Faculty Opinions recommendation of Origin and role of distal visceral endoderm, a group of cells that determines anterior-posterior polarity of the mouse embryo.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.12040956.13193054 ◽

2011 ◽

Author(s):

Guillermo Oliver ◽

Xin Geng

Keyword(s):

Mouse Embryo ◽

Visceral Endoderm ◽

Anterior Posterior

Download Full-text

Hematopoietic induction and respecification of A-P identity by visceral endoderm signaling in the mouse embryo

Development ◽

10.1242/dev.125.24.5009 ◽

1998 ◽

Vol 125 (24) ◽

pp. 5009-5018 ◽

Cited By ~ 11

Author(s):

M. Belaoussoff ◽

S.M. Farrington ◽

M.H. Baron

Keyword(s):

Mouse Embryo ◽

Decisive Role ◽

Primitive Streak ◽

Explant Culture ◽

Cell Contact ◽

Primitive Endoderm ◽

Cell Fates ◽

Posterior Aspect ◽

Anterior Posterior

The anteroposterior axis of the developing embryo becomes morphologically apparent at the onset of gastrulation with the formation of the primitive streak. This structure, where the first mesodermal cells arise, marks the posterior aspect of the embryo. To examine the potential role of non-mesodermal signals in specifying posterior (hematopoietic and endothelial) cell fates in the mouse embryo, we have devised a transgenic explant culture system. We show that interactions between primitive endoderm and adjacent embryonic ectoderm or nascent mesoderm are required early in gastrulation for initiation of hematopoiesis and vasculogenesis. Surprisingly, primitive endoderm signals can respecify anterior (prospective neural) ectoderm to a posterior mesodermal fate, resulting in formation of blood and activation of endothelial markers. Reprogramming of anterior ectoderm does not require cell contact and is effected by stage-dependent, short-range, diffusible signal(s). Therefore, primitive endoderm signaling is a critical early determinant of hematopoietic and vascular development and plays a decisive role in anterior-posterior patterning during mouse embryogenesis.

Download Full-text

Homeotic Genes: Clustering, Modularity, and Diversity

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.718308 ◽

2021 ◽

Vol 9 ◽

Author(s):

Nikhil Hajirnis ◽

Rakesh K. Mishra

Keyword(s):

Genome Engineering ◽

Hox Genes ◽

Hair Follicles ◽

Axis Formation ◽

Homeotic Genes ◽

Holistic View ◽

Evolutionarily Conserved ◽

Genome Assemblies ◽

Anterior Posterior

Hox genes code for transcription factors and are evolutionarily conserved. They regulate a plethora of downstream targets to define the anterior-posterior (AP) body axis of a developing bilaterian embryo. Early work suggested a possible role of clustering and ordering of Hox to regulate their expression in a spatially restricted manner along the AP axis. However, the recent availability of many genome assemblies for different organisms uncovered several examples that defy this constraint. With recent advancements in genomics, the current review discusses the arrangement of Hox in various organisms. Further, we revisit their discovery and regulation in Drosophila melanogaster. We also review their regulation in different arthropods and vertebrates, with a significant focus on Hox expression in the crustacean Parahyale hawaiensis. It is noteworthy that subtle changes in the levels of Hox gene expression can contribute to the development of novel features in an organism. We, therefore, delve into the distinct regulation of these genes during primary axis formation, segment identity, and extra-embryonic roles such as in the formation of hair follicles or misregulation leading to cancer. Toward the end of each section, we emphasize the possibilities of several experiments involving various organisms, owing to the advancements in the field of genomics and CRISPR-based genome engineering. Overall, we present a holistic view of the functioning of Hox in the animal world.

Download Full-text