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

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.

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

Development ◽

10.1242/dev.126.20.4499 ◽

1999 ◽

Vol 126 (20) ◽

pp. 4499-4511 ◽

Cited By ~ 9

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.

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Transforming growth factor-β in the early mouse embryo: Implications for the regulation of muscle formation and implantation

Developmental Genetics ◽

10.1002/dvg.1020140308 ◽

1993 ◽

Vol 14 (3) ◽

pp. 212-224 ◽

Cited By ~ 52

Author(s):

H. G. Slager ◽

W. van Inzen ◽

E. Freund ◽

A. J. M. van den Eijnden-Van Raaij ◽

C. L. Mummery

Keyword(s):

Growth Factor ◽

Mouse Embryo ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β ◽

Early Mouse Embryo ◽

Muscle Formation ◽

Early Mouse

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Growth differentiation factor 11 signals through the transforming growth factor‐β receptor ALK5 to regionalize the anterior–posterior axis

EMBO Reports ◽

10.1038/sj.embor.7400752 ◽

2006 ◽

Vol 7 (8) ◽

pp. 831-837 ◽

Cited By ~ 91

Author(s):

Olov Andersson ◽

Eva Reissmann ◽

Carlos F Ibáñez

Keyword(s):

Growth Factor ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β ◽

Differentiation Factor ◽

Β Receptor ◽

Anterior Posterior ◽

Anterior Posterior Axis

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Intracellular Communication among Morphogen Signaling Pathways during Vertebrate Body Plan Formation

Genes ◽

10.3390/genes11030341 ◽

2020 ◽

Vol 11 (3) ◽

pp. 341

Author(s):

Kimiko Takebayashi-Suzuki ◽

Atsushi Suzuki

Keyword(s):

Growth Factor ◽

Signaling Pathways ◽

Cell Fate ◽

Target Genes ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β ◽

Body Plan ◽

The Body ◽

Fine Tuning ◽

Axis Formation

During embryonic development in vertebrates, morphogens play an important role in cell fate determination and morphogenesis. Bone morphogenetic proteins (BMPs) belonging to the transforming growth factor-β (TGF-β) family control the dorsal–ventral (DV) patterning of embryos, whereas other morphogens such as fibroblast growth factor (FGF), Wnt family members, and retinoic acid (RA) regulate the formation of the anterior–posterior (AP) axis. Activation of morphogen signaling results in changes in the expression of target genes including transcription factors that direct cell fate along the body axes. To ensure the correct establishment of the body plan, the processes of DV and AP axis formation must be linked and coordinately regulated by a fine-tuning of morphogen signaling. In this review, we focus on the interplay of various intracellular regulatory mechanisms and discuss how communication among morphogen signaling pathways modulates body axis formation in vertebrate embryos.

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

Developmental Biology ◽

10.1016/j.ydbio.2008.05.415 ◽

2008 ◽

Vol 319 (2) ◽

pp. 584

Author(s):

Joshua E. Bloomekatz ◽

Andrew Rakeman ◽

Heather Alcorn ◽

Kathryn V. Anderson

Keyword(s):

Mouse Embryo ◽

Axis Formation ◽

Anterior Posterior

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Blastocyst elongation, trophoblastic differentiation, and embryonic pattern formation

Reproduction ◽

10.1530/rep-07-0355 ◽

2008 ◽

Vol 135 (2) ◽

pp. 181-195 ◽

Cited By ~ 76

Author(s):

LeAnn Blomberg ◽

Kazuyoshi Hashizume ◽

Christoph Viebahn

Keyword(s):

Gene Cluster ◽

Transforming Growth Factor ◽

Interleukin 1 ◽

Cell Lineage ◽

Transcriptome Profiling ◽

Primitive Streak ◽

Transforming Growth Factor Β ◽

Cellular Migration ◽

Altered Expression ◽

Porcine Conceptus

The molecular basis of ungulate and non-rodent conceptus elongation and gastrulation remains poorly understood; however, use of state-of-the-art genomic technologies is beginning to elucidate the mechanisms regulating these complicated processes. For instance, transcriptome analysis of elongating porcine concepti indicates that protein synthesis and trafficking, cell growth and proliferation, and cellular morphology are major regulated processes. Furthermore, potential autocrine roles of estrogen and interleukin-1-β in regulating porcine conceptus growth and remodeling and metabolism have become evident. The importance of estrogen in pig is emphasized by the altered expression of essential steroidogenic and trophoblast factors in lagging ovoid concepti. In ruminants, the characteristic mononucleate trophoblast cells differentiate into a second lineage important for implantation, the binucleate trophoblast, and transcriptome profiling of bovine concepti has revealed a gene cluster associated with rapid trophoblast proliferation and differentiation. Gene cluster analysis has also provided evidence of correlated spatiotemporal expression and emphasized the significance of the bovine trophoblast cell lineage and the regulatory mechanism of trophoblast function. As a part of the gastrulation process in the mammalian conceptus, specification of the germ layers and hence definitive body axes occur in advance of primitive streak formation. Processing of the transforming growth factor-β-signaling molecules nodal and BMP4 by specific proteases is emerging as a decisive step in the initial patterning of the pre-gastrulation embryo. The topography of expression of these and other secreted molecules with reference to embryonic and extraembryonic tissues determines their local interaction potential. Their ensuing signaling leads to the specification of axial epiblast and hypoblast compartments through cellular migration and differentiation and, in particular, the specification of the early germ layer tissues in the epiblast via gene expression characteristic of endoderm and mesoderm precursor cells.

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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

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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.

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Mapping cell migrations and fates from a gastruloid model to the human primitive streak

10.1101/616227 ◽

2019 ◽

Author(s):

I. Martyn ◽

E.D. Siggia ◽

A.H. Brivanlou

Keyword(s):

Mouse Embryo ◽

Cell Tracking ◽

Primitive Streak ◽

Parallel Analysis ◽

Self Organization ◽

Model Organisms ◽

Fate Map ◽

Dependent Cell ◽

Early Gastrula ◽

Anterior Posterior

AbstractAlthough fate maps of early gastrula embryos exist for nearly all model organisms, a fate map of the gastrulating human embryo remains elusive. Here we use human gastruloids to piece together part of a rudimentary fate map of the human primitive streak (PS). This is possible because stimulation with differing levels of BMP, WNT, and NODAL leads to self-organization of gastruloids into large and homogenous different subpopulations of endoderm and mesoderm, and comparative parallel analysis of these gastruloids, together with the fate map of the mouse embryo, allows the organization of these subpopulations along an anterior-posterior axis. We also developed a novel cell tracking technique that allowed the detection of robust fate-dependent cell migrations in our gastruloids comparable to those found in the mouse embryo. Taken together, our gastruloid derived fate map and recording of cell migrations provides a first coarse view of the embryonic human PS.

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