The mutual repression between Pax2 and Snail factors regulates the epithelial/mesenchymal state during intermediate mesoderm differentiation

The pronephros is the first renal structure in the embryo, arising after mesenchymal to epithelial transition (MET) of the intermediate mesoderm, where Pax2 induces epithelialization of the mesenchyme. Here we show that, in the early embryo, Snail1 directly represses Pax2 transcription maintaining the intermediate mesoderm in an undifferentiated state. Reciprocally, Pax2 directly represses Snail1 expression to induce MET upon receiving differentiation signals. We also show that BMP7 acts as one such signal by downregulating Snail1 and upregulating Pax2 expression. This, together with the Snail1/Pax2 reciprocal repression, establish a regulatory loop in a defined region along the anteroposterior axis, the bi-stability domain within the transition zone, where differentiation of the neural tube and the somites is known to occur. Thus, we show that the antagonism between Snail1 and Pax2 determines the epithelial/mesenchymal state during the differentiation of the intermediate mesoderm and propose that the bi-stability zone extends to the intermediate mesoderm, synchronizing the differentiation of tissues aligned along the mediolateral embryonic axis.

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Human embryonic stem cells

Journal of Cell Science ◽

10.1242/jcs.113.1.5 ◽

2000 ◽

Vol 113 (1) ◽

pp. 5-10 ◽

Cited By ~ 4

Author(s):

M.F. Pera ◽

B. Reubinoff ◽

A. Trounson

Keyword(s):

Stem Cells ◽

Cell Lines ◽

Embryonal Carcinoma ◽

Es Cells ◽

Embryonic Stem ◽

Early Embryo ◽

Carcinoma Cells ◽

Mouse Es Cells ◽

Undifferentiated State ◽

Human Es Cells

Embryonic stem (ES) cells are cells derived from the early embryo that can be propagated indefinitely in the primitive undifferentiated state while remaining pluripotent; they share these properties with embryonic germ (EG) cells. Candidate ES and EG cell lines from the human blastocyst and embryonic gonad can differentiate into multiple types of somatic cell. The phenotype of the blastocyst-derived cell lines is very similar to that of monkey ES cells and pluripotent human embryonal carcinoma cells, but differs from that of mouse ES cells or the human germ-cell-derived stem cells. Although our understanding of the control of growth and differentiation of human ES cells is quite limited, it is clear that the development of these cell lines will have a widespread impact on biomedical research.

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A role for the vegetally expressed Xenopus gene Mix.1 in endoderm formation and in the restriction of mesoderm to the marginal zone

Development ◽

10.1242/dev.125.13.2371 ◽

1998 ◽

Vol 125 (13) ◽

pp. 2371-2380 ◽

Cited By ~ 13

Author(s):

P. Lemaire ◽

S. Darras ◽

D. Caillol ◽

L. Kodjabachian

Keyword(s):

Marginal Zone ◽

Ectopic Expression ◽

Homeobox Gene ◽

Early Response ◽

Endoderm Differentiation ◽

Head Formation ◽

Mutual Repression ◽

Regulatory Loop ◽

Strong Activator

We have studied the role of the activin immediate-early response gene Mix.1 in mesoderm and endoderm formation. In early gastrulae, Mix.1 is expressed throughout the vegetal hemisphere, including marginal-zone cells expressing the trunk mesodermal marker Xbra. During gastrulation, the expression domains of Xbra and Mix.1 become progressively exclusive as a result of the establishment of a negative regulatory loop between these two genes. This mutual repression is important for the specification of the embryonic body plan as ectopic expression of Mix.1 in the Xbra domain suppresses mesoderm differentiation. The same effect was obtained by overexpressing VP16Mix.1, a fusion protein comprising the strong activator domain of viral VP16 and the homeodomain of Mix.1, suggesting that Mix.1 acts as a transcriptional activator. Mix.1 also has a role in endoderm formation. It cooperates with the dorsal vegetal homeobox gene Siamois to activate the endodermal markers edd, Xlhbox8 and cerberus in animal caps. Conversely, vegetal overexpression of enRMix.1, an antimorphic Mix.1 mutant, leads to a loss of endoderm differentiation. Finally, by targeting enRMix.1 expression to the anterior endoderm, we could test the role of this tissue during embryogenesis and show that it is required for head formation.

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CGEF-1 and CHIN-1 Regulate CDC-42 Activity during Asymmetric Division in the Caenorhabditis elegans Embryo

Molecular Biology of the Cell ◽

10.1091/mbc.e09-01-0060 ◽

2010 ◽

Vol 21 (2) ◽

pp. 266-277 ◽

Cited By ~ 51

Author(s):

Kraig T. Kumfer ◽

Steven J. Cook ◽

Jayne M. Squirrell ◽

Kevin W. Eliceiri ◽

Nina Peel ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Rho Gtpase ◽

Maintenance Phase ◽

Early Embryo ◽

Cell Cortex ◽

Nucleotide Exchange ◽

Cell Stage ◽

Nucleotide Exchange Factor ◽

The One ◽

Regulatory Loop

The anterior–posterior axis of the Caenorhabditis elegans embryo is elaborated at the one-cell stage by the polarization of the partitioning (PAR) proteins at the cell cortex. Polarization is established under the control of the Rho GTPase RHO-1 and is maintained by the Rho GTPase CDC-42. To understand more clearly the role of the Rho family GTPases in polarization and division of the early embryo, we constructed a fluorescent biosensor to determine the localization of CDC-42 activity in the living embryo. A genetic screen using this biosensor identified one positive (putative guanine nucleotide exchange factor [GEF]) and one negative (putative GTPase activating protein [GAP]) regulator of CDC-42 activity: CGEF-1 and CHIN-1. CGEF-1 was required for robust activation, whereas CHIN-1 restricted the spatial extent of CDC-42 activity. Genetic studies placed CHIN-1 in a novel regulatory loop, parallel to loop described previously, that maintains cortical PAR polarity. We found that polarized distributions of the nonmuscle myosin NMY-2 at the cell cortex are independently produced by the actions of RHO-1, and its effector kinase LET-502, during establishment phase and CDC-42, and its effector kinase MRCK-1, during maintenance phase. CHIN-1 restricted NMY-2 recruitment to the anterior during maintenance phase, consistent with its role in polarizing CDC-42 activity during this phase.

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Pax-2 controls multiple steps of urogenital development

Development ◽

10.1242/dev.121.12.4057 ◽

1995 ◽

Vol 121 (12) ◽

pp. 4057-4065 ◽

Cited By ~ 36

Author(s):

M. Torres ◽

E. Gomez-Pardo ◽

G.R. Dressler ◽

P. Gruss

Keyword(s):

Kidney Development ◽

Kidney Diseases ◽

System Development ◽

Collecting Duct ◽

Early Embryo ◽

Urogenital System ◽

Newborn Mice ◽

Intermediate Mesoderm ◽

Mouse Mutants ◽

Urogenital Development

Urogenital system development in mammals requires the coordinated differentiation of two distinct tissues, the ductal epithelium and the nephrogenic mesenchyme, both derived from the intermediate mesoderm of the early embryo. The former give rise to the genital tracts, ureters and kidney collecting duct system, whereas mesenchymal components undergo epithelial transformation to form nephrons in both the mesonephric (embryonic) and metanephric (definitive) kidney. Pax-2 is a transcriptional regulator of the paired-box family and is widely expressed during the development of both ductal and mesenchymal components of the urogenital system. We report here that Pax-2 homozygous mutant newborn mice lack kidneys, ureters and genital tracts. We attribute these defects to dysgenesis of both ductal and mesenchymal components of the developing urogenital system. The Wolffian and Mullerian ducts, precursors of male and female genital tracts, respectively, develop only partially and degenerate during embryogenesis. The ureters, inducers of the metanephros are absent and therefore kidney development does not take place. Mesenchyme of the nephrogenic cord fails to undergo epithelial transformation and is not able to form tubules in the mesonephros. In addition, we show that the expression of specific markers for each of these components is de-regulated in Pax-2 mutants. These data show that Pax-2 is required for multiple steps during the differentiation of intermediate mesoderm. In addition, Pax-2 mouse mutants provide an animal model for human hereditary kidney diseases.

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Laser scanning confocal microscopic analysis of cytoskeletal and nuclear reorganization in live Drosophila embryos

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100146710 ◽

1993 ◽

Vol 51 ◽

pp. 174-175

Author(s):

William Theurkauf

Keyword(s):

Laser Scanning ◽

Microscopic Analysis ◽

Large Cell ◽

Early Embryo ◽

Drosophila Embryo ◽

Cortical Actin ◽

Nuclear Reorganization ◽

Cytoskeletal Elements ◽

Microtubule Structure ◽

Drosophila Embryos

Cell division in eucaryotes depends on coordinated changes in nuclear and cytoskeletal components. In Drosophila melanogaster embryos, the first 13 nuclear divisions occur without cytokinesis. During the final four divisions, nuclei divide in a uniform monolayer at the surface of the embryo. These surface divisions are accompanied by dramatic changes in cortical actin and microtubule structure (Karr and Alberts, 1986), and inhibitor studies indicate that these changes are essential to orderly mitosis (Zalokar and Erk, 1976). Because the early embryo is syncytial, fluorescent probes introduced by microinjection are incorporated in structures associated with all of the nuclei in the blastoderm. In addition, the nuclei divide synchronously every 10 to 20 min. These characteristics make the syncytial blastoderm embryo an excellent system for the analysis of mitotic reorganization of both nuclear and cytoskeletal elements. However, the Drosophila embryo is a large cell, and resolution of cytoskeletal filaments and nuclear structure is hampered by out-of focus signal.

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