Promoting notochord fate and repressing muscle development in zebrafish axial mesoderm

Development ◽  
1998 ◽  
Vol 125 (8) ◽  
pp. 1397-1406 ◽  
Author(s):  
S.L. Amacher ◽  
C.B. Kimmel
Keyword(s):  
Cell Fate ◽  
Double Mutant ◽  
Muscle Development ◽  
Genetic Interaction ◽  
Embryonic Cells ◽  
Wild Type ◽  
Environmental Signals ◽  
Cell Fate Decisions ◽  
Muscle Genes ◽  
Midline Cells

Cell fate decisions in early embryonic cells are controlled by interactions among developmental regulatory genes. Zebrafish floating head mutants lack a notochord; instead, muscle forms under the neural tube. As shown previously, axial mesoderm in floating head mutant gastrulae fails to maintain expression of notochord genes and instead expresses muscle genes. Zebrafish spadetail mutant gastrulae have a nearly opposite phenotype; notochord markers are expressed in a wider domain than in wild-type embryos and muscle marker expression is absent. We examined whether these two phenotypes revealed an antagonistic genetic interaction by constructing the double mutant. Muscle does not form in the spadetail;floating head double mutant midline, indicating that spadetail function is required for floating head mutant axial mesoderm to transfate to muscle. Instead, the midline of spadetail;floating head double mutants is greatly restored compared to that of floating head mutants; the floor plate is almost complete and an anterior notochord develops. In addition, we find that floating head mutant cells can make both anterior and posterior notochord when transplanted into a wild-type host, showing that enviromental signals can override the predisposition of floating head mutant midline cells to make muscle. Taken together, these results suggest that repression of spadetail function by floating head is critical to promote notochord fate and prevent midline muscle development, and that cells can be recruited to the notochord by environmental signals.

scholarly journals The Roles of Chromatin Accessibility in Regulating the Candida albicans White-Opaque Phenotypic Switch

2021 ◽  
Vol 7 (1) ◽  
pp. 37
Author(s):  
Mohammad N. Qasim ◽  
Ashley Valle Arevalo ◽  
Clarissa J. Nobile ◽  
Aaron D. Hernday
Keyword(s):  
Candida Albicans ◽  
Cell Fate ◽  
Cell Types ◽  
Chromatin Accessibility ◽  
Phenotypic Switching ◽  
Phenotypic Switch ◽  
Chromatin Remodelers ◽  
Environmental Signals ◽  
Cell Fate Decisions ◽  
Simple Model System

Candida albicans, a diploid polymorphic fungus, has evolved a unique heritable epigenetic program that enables reversible phenotypic switching between two cell types, referred to as “white” and “opaque”. These cell types are established and maintained by distinct transcriptional programs that lead to differences in metabolic preferences, mating competencies, cellular morphologies, responses to environmental signals, interactions with the host innate immune system, and expression of approximately 20% of genes in the genome. Transcription factors (defined as sequence specific DNA-binding proteins) that regulate the establishment and heritable maintenance of the white and opaque cell types have been a primary focus of investigation in the field; however, other factors that impact chromatin accessibility, such as histone modifying enzymes, chromatin remodelers, and histone chaperone complexes, also modulate the dynamics of the white-opaque switch and have been much less studied to date. Overall, the white-opaque switch represents an attractive and relatively “simple” model system for understanding the logic and regulatory mechanisms by which heritable cell fate decisions are determined in higher eukaryotes. Here we review recent discoveries on the roles of chromatin accessibility in regulating the C. albicans white-opaque phenotypic switch.

scholarly journals Expression of an activated rasD gene changes cell fate decisions during Dictyostelium development.

1997 ◽  
Vol 8 (2) ◽  
pp. 303-312 ◽  
Author(s):  
S A Louis ◽  
G B Spiegelman ◽  
G Weeks
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Cell Mass ◽  
Cell Formation ◽  
Specific Gene ◽  
Wild Type ◽  
Multicellular Development ◽  
Cell Fate Decisions ◽  
Prespore Cell

It has been previously demonstrated that the expression of an activated rasD gene in wild-type Dictyostelium cells results in formation of aggregates with multitips, instead of the normal single tips, and a block in further development. In an attempt to better understand the role of activated RasD development, we examined cell-type-specific gene expression in a strain stably expressing high levels of RasD[G12T]. We found that the expression of prestalk cell-specific genes ecmA and tagB was markedly enhanced, whereas the expression of the prespore cell-specific gene cotC was reduced to very low levels. When the fate of cells in the multitipped aggregate was monitored with an ecmA/lacZ fusion, it appeared that most of the cells eventually adopted prestalk gene expression characteristics. When mixtures of the [G12T]rasD cells and Ax3 cells were induced to differentiate, chimeric pseudoplasmodia were not formed. Thus, although the [G12T]rasD transformant had a marked propensity to form prestalk cells, it could not supply the prestalk cell population when mixed with wild-type cells. Both stalk and spore cell formation occurred in low cell density monolayers of the [G12T]rasD strain, suggesting that at least part of the inhibition of stalk and spore formation during multicellular development involved inhibitory cell interactions within the cell mass. Models for the possible role of rasD in development are discussed.

scholarly journals Photoperiod sensing of the circadian clock is controlled by EARLY FLOWERING 3 and GIGANTEA

2018 ◽  
Author(s):  
Muhammad Usman Anwer ◽  
Amanda Davis ◽  
Seth Jon Davis ◽  
Marcel Quint
Keyword(s):  
Circadian Clock ◽  
Double Mutant ◽  
Genetic Interaction ◽  
Loss Of Function ◽  
Cellular Mechanisms ◽  
Environmental Signals ◽  
Photoperiodic Flowering ◽  
Oscillator Function ◽  
Key Genes ◽  
Central Oscillator

SummaryELF3 and GI are two important components of the Arabidopsis circadian clock. They are not only essential for the oscillator function but are also pivotal in mediating light inputs to the oscillator. Lack of either results in a defective oscillator causing severely compromised output pathways, such as photoperiodic flowering and hypocotyl elongation. Although single loss of function mutants of ELF3 and GI have been well-studied, their genetic interaction remains unclear. We generated an elf3 gi double mutant to study their genetic relationship in clock-controlled growth and phase transition phenotypes. We found that ELF3 and GI repress growth differentially during the night and the day, respectively. Circadian clock assays revealed that ELF3 and GI are essential Zeitnehmers that enable the oscillator to synchronize the endogenous cellular mechanisms to external environmental signals. In their absence, the circadian oscillator fails to synchronize to the light-dark cycles even under diurnal conditions. Consequently, clock-mediated photoperiod-responsive growth and development is completely lost in plants lacking both genes, suggesting that ELF3 and GI together convey photoperiod sensing to the central oscillator. Since ELF3 and GI are conserved across flowering plants and represent important breeding and domestication targets, our data highlight the possibility of developing photoperiod-insensitive crops by adjusting the allelic combination of these two key genes.One sentence summaryELF3 and GI are essential for circadian clock mediated photoperiod sensing.

scholarly journals Oxygen-generated spatial distribution of cell population links to p53 status

2019 ◽  
Author(s):  
Shashank Taxak ◽  
Uttam Pati
Keyword(s):  
Spatial Distribution ◽  
Cell Fate ◽  
Cell Population ◽  
Oxygen Sensor ◽  
Dynamic State ◽  
Specific Cell ◽  
Wild Type ◽  
Cell Fate Decisions ◽  
Wide Range ◽  
Wild Type P53

ABSTRACTLow oxygen induces wild type p53 inactivation and selects for mutant-like p53 phenotypes for aggressive tumor growth. Recently, we have shown wild type p53 as a cellular oxygen-sensor that operates in switch-like fashion to transform its characters of a tumor suppressor or promoter in a gradient of hypoxia. However, it is unclear how hypoxic tumors select for wild type p53 phenotypes for oxygen-sensitive responses. Here, we show that oxygen-generated spatial distribution of the cell population induces p53 phenotype-specific survival or death. We have found that a dynamic state of spatial scatters or clustering patterns of cell populations favor the survival of wild type more than the mutant phenotypes in a wide range of oxygen fluctuation by affecting p53 subcellular localization. Our results demonstrate how spatial distribution could function to establish wild type p53-mediated oxygen sensing and cell fate decisions in a cell population with heterogeneous p53 allele status. We anticipate that such behavior of cells in a gradient of oxygen can be utilized by the hypoxic tumors to maintain distinct p53 alleles and determine the release and metastasis of single or clustered circulating tumor cells (CTCs).Summary sentenceOxygen variation results in p53 phenotype-specific cell fate via the spatial distribution pattern of the cell population

scholarly journals A single-cell resolved cell-cell communication model explains lineage commitment in hematopoiesis

Development ◽  
2021 ◽  
Vol 148 (24) ◽  
Author(s):  
Megan K. Rommelfanger ◽  
Adam L. MacLean
Keyword(s):  
Cell Fate ◽  
Cell Communication ◽  
Communication Model ◽  
Cell Fate Decision ◽  
Cell Coupling ◽  
Environmental Signals ◽  
Cell Fate Decisions ◽  
Wide Range ◽  
Fate Decision ◽  
Cell Cell

ABSTRACT Cells do not make fate decisions independently. Arguably, every cell-fate decision occurs in response to environmental signals. In many cases, cell-cell communication alters the dynamics of the internal gene regulatory network of a cell to initiate cell-fate transitions, yet models rarely take this into account. Here, we have developed a multiscale perspective to study the granulocyte-monocyte versus megakaryocyte-erythrocyte fate decisions. This transition is dictated by the GATA1-PU.1 network: a classical example of a bistable cell-fate system. We show that, for a wide range of cell communication topologies, even subtle changes in signaling can have pronounced effects on cell-fate decisions. We go on to show how cell-cell coupling through signaling can spontaneously break the symmetry of a homogenous cell population. Noise, both intrinsic and extrinsic, shapes the decision landscape profoundly, and affects the transcriptional dynamics underlying this important hematopoietic cell-fate decision-making system. This article has an associated ‘The people behind the papers’ interview.

CELLULAR FEEDBACK NETWORKS AND THEIR RESILIENCE AGAINST MUTATIONS

2021 ◽  
pp. 1-50
Author(s):  
LORA D. BAILEY ◽  
NATALIA L. KOMAROVA
Keyword(s):  
Cell Fate ◽  
Feedback Loops ◽  
Wild Type ◽  
Feedback Parameter ◽  
Cell Fate Decisions ◽  
Slowing Down ◽  
Unlimited Growth ◽  
Type Population ◽  
Control Feedback ◽  
Feedback Networks

Many tissues undergo a steady turnover, where cell divisions are on average balanced with cell deaths. Cell fate decisions such as stem cell (SC) differentiations, proliferations, or differentiated cell (DC) deaths, may be controlled by cell populations through cell-to-cell signaling. Here, we examine a class of mathematical models of turnover in SC lineages to understand engineering design principles of control (feedback) loops, that may operate in such systems. By using ordinary differential equations that describe the co-dynamics of SCs and DCs, we study the effect of different types of mutations that interfere with feedback present within cellular networks. For instance, we find that mutants that do not participate in feedback are less dangerous in the sense that they will not rise from low numbers, whereas mutants that do not respond to feedback signals could rise and replace the wild-type population. Additionally, we asked if different feedback networks can have different degrees of resilience against such mutations. We found that all minimal networks, that is networks consisting of exactly one feedback loop that is sufficient for homeostatic stability of the wild-type population, are equally vulnerable. Mutants with a weakened/eliminated feedback parameter might expand from lower numbers and either enter unlimited growth or reach an equilibrium with an increased number of SCs and DCs. Therefore, from an evolutionary viewpoint, it appears advantageous to combine feedback loops, creating redundant feedback networks. Interestingly, from an engineering prospective, not all such redundant systems are equally resilient. For some of them, any mutation that weakens/eliminates one of the loops will lead to a population growth of SCs. For others, the population of SCs can actually shrink as a result of “cutting” one of the loops, thus slowing down further unwanted transformations.

Altered epidermal growth factor-like sequences provide evidence for a role of Notch as a receptor in cell fate decisions

Development ◽  
1993 ◽  
Vol 117 (3) ◽  
pp. 1113-1123 ◽  
Author(s):  
P. Heitzler ◽  
P. Simpson
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Fate ◽  
Cell Interactions ◽  
Signalling Pathway ◽  
Neural Precursor ◽  
Wild Type ◽  
Cell Fate Decisions ◽  
Epidermal Growth

In Drosophila each neural precursor is chosen from a group of cells through cell interactions mediated by Notch and Delta which may function as receptor and ligand (signal), respectively, in a lateral signalling pathway. The cells of a group are equipotential and express both Notch and Delta. Hyperactive mutant Notch molecules, (Abruptex), probably have an enhanced affinity for the ligand. When adjacent to wild-type cells, cells bearing the Abruptex proteins are unable to produce the signal. It is suggested that in addition to the binding of Notch molecules on one cell to the Delta molecules of opposing cells, the Notch and Delta proteins on the surface of the same cell may interact. Binding between a cell's own Notch and Delta molecules would alter the availability of these proteins to interact with their counterparts on adjacent cells.

Physiologically Significant Genetic Interaction between STAT5 and Gab2 during Normal and Pathologic Hematopoiesis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 87-87
Author(s):  
Geqiang Li ◽  
Zhengqi Wang ◽  
Yi Zhang ◽  
Eleonora Haviernikova ◽  
William Tse ◽  
...  
Keyword(s):  
Double Mutant ◽  
Genetic Interaction ◽  
Central Vein ◽  
Physical Interaction ◽  
Myeloproliferative Disease ◽  
Wild Type ◽  
Double Knockout ◽  
Hematopoietic Stem ◽  
Constitutively Active

Abstract Signal transducer and activator of transcription-5 (STAT5) is critical for normal hematopoiesis and its dysregulated activation is associated with hematologic disease in mice and humans. Recently, a constitutively active mutant of STAT5 (STAT5aS711F, also called STAT5a*6) was shown to bind a cytosolic Gab2 complex leading to increased Akt activation. We have also found that co-transfection of erythropoietin (EPO) receptor along with STAT5a or STAT5a*6 in 293T cells leads to STAT5/Gab2 physical interaction in response to EPO. However, the physiological significance in vivo is not known. Therefore, we asked whether STAT5 and Gab2 provide overlapping/non-overlapping, or cooperative/additive functions in fetal and adult hematopoiesis. To do this, we generated and crossed STAT5ab+/nullGab2+/− mice to yield STAT5abnull/nullGab2−/ − double knockout embryos. At E14.5, a normal Mendelian ratio (6/94) of double mutant was obtained. So far no double mutant embryos at E18.5 (0/16) have been detected. Histology analyses of mutant embryos are pending. At E14.5 STAT5abnull/nullGab2−/ − total CFU-C frequency was reduced to 11–29% of normal (N=3) compared with STAT5 or Gab2 single mutants which ranged 63–100%. We also tested for interaction between adult STAT5ab+/null and Gab2−/ − genotype. Both STAT5ab+/null and Gab2−/ − mice and their STAT5ab+/nullGab2−/ − cross were born at normal Mendelian ratio. STAT5ab+/nullGab2−/ − mice had 57% of normal absolute numbers of IgM+/B220+ B cells but all other lineages were comparable to the single mutants. However, in two independent transplant experiments, STAT5ab+/null and Gab2−/ − bone marrow (BM) had competitive multilineage hematopoietic stem cell repopulating defects averaging 36% and 18% of wild-type respectively. Notably, STAT5ab+/nullGab2−/ − BM cells had an average 6% of wild-type engraftment, which is exactly as predicted for additive non-redundant defects (0.36 x 0.18). Next, we performed experiments using persistent high level STAT5 activation using retroviral-mediated expression of MSCV/STAT5a*6-IRES-GFP. To determine whether myeloproliferative disease (MPD) driven by constitutively active STAT5 utilizes Gab2 interactions, wild-type or Gab2−/ − BM cells were transduced and transplanted into recipient mice followed by analysis of MPD. We observed good levels of gene transfer (GFP+ cells) using the IRES-GFP control or STAT5a*6 vector for either wild-type or Gab2−/ − BM (33–70%), indicating no adverse effects of Gab2 deficiency on retroviral transduction and transplantation. STAT5a*6 vector transduced into wild-type BM increased the frequency of Gr-1+Mac-1+ cells (8-fold) in peripheral blood and disrupted the splenic architecture of transplanted mice. In the liver the architecture remained intact despite perivascular infiltration of the portal track, central vein, and lobules with granulocytic lineage cells in different stages of differentiation. Interestingly, the expansion of the Gr-1+Mac-1+ population was 5- to 6-fold reduced in the absence of Gab2 and led to 2- to 3-fold reduced spleen weights. This attenuation modestly improved survival, although both groups of mice died of MPD. A second independent cohort of mice has been transplanted. Overall, these data indicate that STAT5 and Gab2 play critical non-redundant functions in normal and pathologic hematopoiesis and suggest that combined STAT5/Gab2 inhibition strategies might lead to at least an additive therapeutic benefit.

scholarly journals mTOR signaling at the crossroads of environmental signals and T‐cell fate decisions

2020 ◽  
Vol 295 (1) ◽  
pp. 15-38 ◽  
Author(s):  
Hongling Huang ◽  
Lingyun Long ◽  
Peipei Zhou ◽  
Nicole M. Chapman ◽  
Hongbo Chi
Keyword(s):  
T Cell ◽  
Cell Fate ◽  
Mtor Signaling ◽  
Environmental Signals ◽  
Cell Fate Decisions

scholarly journals Early cell fate decisions in the mouse embryo

Reproduction ◽  
2013 ◽  
Vol 145 (3) ◽  
pp. R65-R80 ◽  
Author(s):  
Néstor Saiz ◽  
Berenika Plusa
Keyword(s):  
Cell Differentiation ◽  
Cell Fate ◽  
Mouse Embryo ◽  
Molecular Mechanisms ◽  
Current Evidence ◽  
Cellular Interaction ◽  
Embryonic Cells ◽  
Developmental Potential ◽  
Cell Fate Decisions ◽  
Preimplantation Mouse

During mammalian preimplantation development, the fertilised egg gives rise to a group of pluripotent embryonic cells, the epiblast, and to the extraembryonic lineages that support the development of the foetus during subsequent phases of development. This preimplantation period not only accommodates the first cell fate decisions in a mammal's life but also the transition from a totipotent cell, the zygote, capable of producing any cell type in the animal, to cells with a restricted developmental potential. The cellular and molecular mechanisms governing the balance between developmental potential and lineage specification have intrigued developmental biologists for decades. The preimplantation mouse embryo offers an invaluable system to study cell differentiation as well as the emergence and maintenance of pluripotency in the embryo. Here we review the most recent findings on the mechanisms controlling these early cell fate decisions. The model that emerges from the current evidence indicates that cell differentiation in the preimplantation embryo depends on cellular interaction and intercellular communication. This strategy underlies the plasticity of the early mouse embryo and ensures the correct specification of the first mammalian cell lineages.

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