scholarly journals Abnormalities of the Genitourinary Tract in Female Mice Lacking GATA5

2000 ◽  
Vol 20 (14) ◽  
pp. 5256-5260 ◽  
Author(s):  
Jeffery D. Molkentin ◽  
Kevin M. Tymitz ◽  
James A. Richardson ◽  
Eric N. Olson
Keyword(s):  
Cell Fate ◽  
Null Allele ◽  
Cell Fate Specification ◽  
Mammalian Development ◽  
Gata Factor ◽  
Genitourinary System ◽  
Gata Factors ◽  
Developing Heart

ABSTRACT Members of the GATA family of transcription factors play important roles in cell fate specification, differentiation, and morphogenesis during mammalian development. GATA5, the only one of the six vertebrate GATA factor genes not yet inactivated in mice, is expressed in a pattern that overlaps with but is distinct from that of other GATA factor genes. During mouse embryogenesis, GATA5 is expressed first in the developing heart and subsequently in the lung, vasculature, and genitourinary system. To investigate the function of GATA5 in vivo, we created mice homozygous for a GATA5 null allele. Homozygous mutants were viable and fertile, but females exhibited pronounced genitourinary abnormalities that included vaginal and uterine defects and hypospadias. In contrast, the genitourinary system was unaffected in male GATA5 mutants. These results reveal a specific role of GATA5 in development of the female genitourinary system and suggest that other GATA factors may have functions overlapping those of GATA5 in other tissues.

scholarly journals A Genome-Wide RNA Interference Screen Identifies a Differential Role of the Mediator CDK8 Module Subunits for GATA/ RUNX-Activated Transcription in Drosophila

2010 ◽  
Vol 30 (11) ◽  
pp. 2837-2848 ◽  
Author(s):  
Vanessa Gobert ◽  
Dani Osman ◽  
Stéphanie Bras ◽  
Benoit Augé ◽  
Muriel Boube ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Rna Interference ◽  
Cell Fate ◽  
Gata Factor ◽  
Hematopoietic System ◽  
Crystal Cell ◽  
Genome Wide ◽  
A Genome

ABSTRACT Transcription factors of the RUNX and GATA families play key roles in the control of cell fate choice and differentiation, notably in the hematopoietic system. During Drosophila hematopoiesis, the RUNX factor Lozenge and the GATA factor Serpent cooperate to induce crystal cell differentiation. We used Serpent/Lozenge-activated transcription as a paradigm to identify modulators of GATA/RUNX activity by a genome-wide RNA interference screen in cultured Drosophila blood cells. Among the 129 factors identified, several belong to the Mediator complex. Mediator is organized in three modules plus a regulatory “CDK8 module,” composed of Med12, Med13, CycC, and Cdk8, which has long been thought to behave as a single functional entity. Interestingly, our data demonstrate that Med12 and Med13 but not CycC or Cdk8 are essential for Serpent/Lozenge-induced transactivation in cell culture. Furthermore, our in vivo analysis of crystal cell development show that, while the four CDK8 module subunits control the emergence and the proliferation of this lineage, only Med12 and Med13 regulate its differentiation. We thus propose that Med12/Med13 acts as a coactivator for Serpent/Lozenge during crystal cell differentiation independently of CycC/Cdk8. More generally, we suggest that the set of conserved factors identified herein may regulate GATA/RUNX activity in mammals.

scholarly journals Transitions in cell potency during early mouse development are driven by Notch

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Sergio Menchero ◽  
Isabel Rollan ◽  
Antonio Lopez-Izquierdo ◽  
Maria Jose Andreu ◽  
Julio Sainz de Aja ◽  
...  
Keyword(s):  
Cell Fate ◽  
Cell Types ◽  
Mammalian Development ◽  
Mouse Development ◽  
Cell Stage ◽  
Notch Signalling Pathway ◽  
Gradual Loss ◽  
Early Mouse

The Notch signalling pathway plays fundamental roles in diverse developmental processes in metazoans, where it is important in driving cell fate and directing differentiation of various cell types. However, we still have limited knowledge about the role of Notch in early preimplantation stages of mammalian development, or how it interacts with other signalling pathways active at these stages such as Hippo. By using genetic and pharmacological tools in vivo, together with image analysis of single embryos and pluripotent cell culture, we have found that Notch is active from the 4-cell stage. Transcriptomic analysis in single morula identified novel Notch targets, such as early naïve pluripotency markers or transcriptional repressors such as TLE4. Our results reveal a previously undescribed role for Notch in driving transitions during the gradual loss of potency that takes place in the early mouse embryo prior to the first lineage decisions.

scholarly journals Transitions in cell potency during early mouse development are driven by Notch

2018 ◽  
Author(s):  
Sergio Menchero ◽  
Antonio Lopez-Izquierdo ◽  
Isabel Rollan ◽  
Julio Sainz de Aja ◽  
Maria Jose Andreu ◽  
...  
Keyword(s):  
Cell Fate ◽  
Cell Types ◽  
Mammalian Development ◽  
Mouse Development ◽  
Cell Stage ◽  
Notch Signalling Pathway ◽  
Gradual Loss ◽  
Early Mouse

AbstractThe Notch signalling pathway plays fundamental roles in diverse developmental processes in metazoans, where it is important in driving cell fate and directing differentiation of various cell types. However, we still have limited knowledge about the role of Notch in early preimplantation stages of mammalian development, or how it interacts with other signalling pathways active at these stages such as Hippo. By using genetic and pharmacological tools in vivo, together with image analysis of single embryos and pluripotent cell culture, we have found that Notch is active from the 4-cell stage. Transcriptomic analysis in single morula identified novel Notch targets, such as early naïve pluripotency markers or transcriptional repressors such as TLE4. Our results reveal a previously undescribed role for Notch in driving transitions during the gradual loss of potency that takes place in the early mouse embryo prior to the first lineage decisions.

Targeted disruption of the murine junD gene results in multiple defects in male reproductive function

Development ◽  
2000 ◽  
Vol 127 (1) ◽  
pp. 143-153 ◽  
Author(s):  
D. Thepot ◽  
J.B. Weitzman ◽  
J. Barra ◽  
D. Segretain ◽  
M.G. Stinnakre ◽  
...  
Keyword(s):  
Reproductive Function ◽  
Postnatal Growth ◽  
Mrna Levels ◽  
Targeted Disruption ◽  
Male Reproductive Function ◽  
Developing Heart ◽  
Redundant Functions ◽  
Transcription Factor Complex

JunD is one of three mammalian Jun proteins that contribute to the AP-1 transcription factor complex. Distinct regulation and functions have been proposed for each Jun member, but less is known about the biological functions of each of these proteins in vivo. To investigate the role of JunD, we have inactivated the murine gene by replacement with a bacterial lacZ reporter gene. Embryonic JunD expression was initially detected in the developing heart and cardiovascular system. Subsequent broadening phases of JunD expression were observed during embryonic development and expression in the adult was widespread in many tissues and cell lineages. Mutant animals lack JunD mRNA and protein and showed no evidence of upregulation of c-Jun and JunB mRNA levels. In contrast to the other two Jun members, homozygous JunD−/− mutant animals were viable and appeared healthy. However, homozygous JunD−/− animals showed a reduced postnatal growth. Furthermore, JunD−/− males exhibited multiple age-dependent defects in reproduction, hormone imbalance and impaired spermatogenesis with abnormalities in head and flagellum sperm structures. No defects in fertility were observed in JunD−/− female animals. These results provide evidence for redundant functions for members of the Jun family during development and specific functions for JunD in male reproductive function.

GATA transcription factors as potentiators of gut endoderm differentiation

Development ◽  
1998 ◽  
Vol 125 (24) ◽  
pp. 4909-4917 ◽  
Author(s):  
P. Bossard ◽  
K.S. Zaret
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Site Occupancy ◽  
Gata Factor ◽  
Transcriptional Enhancer ◽  
Gata Factors ◽  
Endoderm Differentiation ◽  
Albumin Gene ◽  
Gut Endoderm

Gene inactivation studies have shown that members of the GATA family of transcription factors are critical for endoderm differentiation in mice, flies and worms, yet how these proteins function in such a conserved developmental context has not been understood. We use in vivo footprinting of mouse embryonic endoderm cells to show that a DNA-binding site for GATA factors is occupied on a liver-specific, transcriptional enhancer of the serum albumin gene. GATA site occupancy occurs in gut endoderm cells at their pluripotent stage: the cells have the potential to initiate tissue development but they have not yet been committed to express albumin or other tissue-specific genes. The GATA-4 isoform accounts for about half of the nuclear GATA-factor-binding activity in the endoderm. GATA site occupancy persists during hepatic development and is necessary for the activity of albumin gene enhancer. Thus, GATA factors in the endoderm are among the first to bind essential regulatory sites in chromatin. Binding occurs prior to activation of gene expression, changes in cell morphology or functional commitment that would indicate differentiation. We suggest that GATA factors at target sites in chromatin may generally help potentiate gene expression and tissue specification in metazoan endoderm development.

Genes necessary for C. elegans cell and growth cone migrations

Development ◽  
1997 ◽  
Vol 124 (9) ◽  
pp. 1831-1843 ◽  
Author(s):  
W.C. Forrester ◽  
G. Garriga
Keyword(s):  
Cell Fate ◽  
Single Gene ◽  
Growth Cones ◽  
Cell Fate Specification ◽  
Fate Specification ◽  
C Elegans ◽  
Final Destination ◽  
Multiple Cell

The migrations of cells and growth cones contribute to form and pattern during metazoan development. To study the mechanisms that regulate cell motility, we have screened for C. elegans mutants defective in the posteriorly directed migrations of the canal-associated neurons (CANs). Here we describe 14 genes necessary for CAN cell migration. Our characterization of the mutants has led to three conclusions. First, the mutations define three gene classes: genes necessary for cell fate specification, genes necessary for multiple cell migrations and a single gene necessary for final positioning of migrating cells. Second, cell interactions between the CAN and HSN, a neuron that migrates anteriorly to a position adjacent to the CAN, control the final destination of the HSN cell body. Third, C. elegans larval development requires the CANs. In the absence of CAN function, larvae arrest development, with excess fluid accumulating in their pseudocoeloms. This phenotype may reflect a role of the CANs in osmoregulation.

Suppression of GATA factor activity causes axis duplication in Xenopus

Development ◽  
1998 ◽  
Vol 125 (23) ◽  
pp. 4595-4605 ◽  
Author(s):  
T.G. Sykes ◽  
A.R. Rodaway ◽  
M.E. Walmsley ◽  
R.K. Patient
Keyword(s):  
Cell Fate ◽  
Homeobox Gene ◽  
Dominant Negative ◽  
Gata Factor ◽  
Dorsoventral Axis ◽  
Morphogenetic Protein ◽  
Head Formation ◽  
Bmp Signalling ◽  
Bmp Antagonist

In Xenopus, the dorsoventral axis is patterned by the interplay between active signalling in ventral territories, and secreted antagonists from Spemann's organiser. Two signals are important in ventral cells, bone morphogenetic protein-4 (BMP-4) and Wnt-8. BMP-4 plays a conserved role in patterning the vertebrate dorsoventral axis, whilst the precise role of Wnt-8 and its relationship with BMP-4, are still unclear. Here we have investigated the role played by the GATA family of transcription factors, which are expressed in ventral mesendoderm during gastrulation and are required for the differentiation of blood and endodermal tissues. Injection ventrally of a dominant-interfering GATA factor (called G2en) induced the formation of secondary axes that phenocopy those induced by the dominant-negative BMP receptor. However, unlike inhibiting BMP signalling, inhibiting GATA activity in the ectoderm does not lead to neuralisation. In addition, analysis of gene expression in G2en injected embryos reveals that at least one known target gene for BMP-4, the homeobox gene Vent-2, is unaffected. In contrast, the expression of Wnt-8 and the homeobox gene Vent-1 is suppressed by G2en, whilst the organiser-secreted BMP antagonist chordin becomes ectopically expressed. These data therefore suggest that GATA activity is essential for ventral cell fate and that subsets of ventralising and dorsalising genes require GATA activity for their expression and suppression, respectively. Finally, using G2en, we show that suppression of Wnt-8 expression, in conjunction with blocked BMP signalling, does not lead to head formation, suggesting that the head-suppressing Wnt signal may not be Wnt-8.

Stem Cell Fate Specification: Role of Master Regulatory Switch Transcription Factor PU.1 in Differential Hematopoiesis

2005 ◽  
Vol 14 (2) ◽  
pp. 140-152 ◽  
Author(s):  
Gurudutta U. Gangenahalli ◽  
Pallavi Gupta ◽  
Daman Saluja ◽  
Yogesh K. Verma ◽  
Vimal Kishore ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Stem Cell ◽  
Cell Fate ◽  
Cell Fate Specification ◽  
Stem Cell Fate ◽  
Fate Specification

A Dual Proto-Oncogenic and Tumor Suppressive Role of LRF/POKEMON In Hemopoietic Malignancies through Control of Cell Fate Decision

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. SCI-14-SCI-14
Author(s):  
Pier Paolo Pandolfi
Keyword(s):  
Cell Fate ◽  
Cellular Differentiation ◽  
Conflicts Of Interest ◽  
Human Cancer ◽  
Cellular Transformation ◽  
Related Factor ◽  
Cancer Genes ◽  
Cell Fate Decisions

Abstract Abstract SCI-14 LRF (Leukemia/lymphoma-related factor, also known as POKEMON) is a member of the POZ and Kruppel (POK) family of transcription factors. LRF has been shown to play an essential role in embryonic development and to act as a master regulator of cellular differentiation in virtually any tissue where it is found expressed, including the hemopoietic compartment. As we will discuss, LRF inactivation in the mouse blocks cellular differentiation in both myeloid/erythroid and lymphoid compartments. On the other hand, LRF has been shown to possess a potent proto-oncogenic activity both in vitro and in vivo. In fact, LRF itself can transform primary cells in combination with known oncogenes and is also essential for cellular transformation of mouse embryonic fibroblasts. In addition, overexpression of LRF in immature B and T progenitor cells in vivo in the mouse lead to lethal precursor T-cell lymphoblastic lymphoma/leukemia. In agreement with this notion, LRF is aberrantly expressed in a variety of human cancers, including diffuse large B cell and follicular lymphomas, but also ovarian and breast cancers. Further, the LRF gene is found amplified in a subset of non-small cell lung cancers (NSCLCs), illustrating a direct role in human cancer. However, we speculated that due to the key role of LRF in cell fate decisions, LRF/POKEMON loss could also contribute to tumorigenesis by blocking cellular differentiation. We will discuss provocative in vivo data in support of the notion that LRF/POKEMON can indeed act as a bona fide tumor suppressor representing a compelling example of two-faced cancer genes. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The role of the Rx homeobox gene in retinal progenitor proliferation and cell fate specification

2018 ◽  
Vol 151 ◽  
pp. 18-29 ◽  
Author(s):  
H.M. Rodgers ◽  
V.J. Huffman ◽  
V.A. Voronina ◽  
M. Lewandoski ◽  
P.H. Mathers
Keyword(s):  
Cell Fate ◽  
Homeobox Gene ◽  
Cell Fate Specification ◽  
Fate Specification ◽  
Retinal Progenitor
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