scholarly journals MEX-3 interacting proteins link cell polarity to asymmetric gene expression in Caenorhabditis elegans

Development ◽  
2002 ◽  
Vol 129 (3) ◽  
pp. 747-759 ◽  
Author(s):  
Nancy N. Huang ◽  
Darcy E. Mootz ◽  
Albertha J. M. Walhout ◽  
Marc Vidal ◽  
Craig P. Hunter
Keyword(s):  
Cell Fate ◽  
Spatial Information ◽  
Zinc Finger Protein ◽  
Early Embryo ◽  
Rna Recognition Motif ◽  
Homeodomain Protein ◽  
Interacting Proteins ◽  
Cell Stage ◽  
C Elegans ◽  
Temporal And Spatial

The KH domain protein MEX-3 is central to the temporal and spatial control of PAL-1 expression in the C. elegans early embryo. PAL-1 is a Caudal-like homeodomain protein that is required to specify the fate of posterior blastomeres. While pal-1 mRNA is present throughout the oocyte and early embryo, PAL-1 protein is expressed only in posterior blastomeres, starting at the four-cell stage. To better understand how PAL-1 expression is regulated temporally and spatially, we have identified MEX-3 interacting proteins (MIPs) and characterized in detail two that are required for the patterning of PAL-1 expression. RNA interference of MEX-6, a CCCH zinc-finger protein, or SPN-4, an RNA recognition motif protein, causes PAL-1 to be expressed in all four blastomeres starting at the four-cell stage. Genetic analysis of the interactions between these mip genes and the par genes, which provide polarity information in the early embryo, defines convergent genetic pathways that regulate MEX-3 stability and activity to control the spatial pattern of PAL-1 expression. These experiments suggest that par-1 and par-4 affect distinct processes. par-1 is required for many aspects of embryonic polarity, including the restriction of MEX-3 and MEX-6 activity to the anterior blastomeres. We find that PAL-1 is not expressed in par-1 mutants, because MEX-3 and MEX-6 remain active in the posterior blastomeres. The role of par-4 is less well understood. Our analysis suggests that par-4 is required to inactivate MEX-3 at the four-cell stage. Thus, PAL-1 is not expressed in par-4 mutants because MEX-3 remains active in all blastomeres. We propose that MEX-6 and SPN-4 act with MEX-3 to translate the temporal and spatial information provided by the early acting par genes into the asymmetric expression of the cell fate determinant PAL-1.

The maternal genespn-4encodes a predicted RRM protein required for mitotic spindle orientation and cell fate patterning in earlyC. elegansembryos

Development ◽  
2001 ◽  
Vol 128 (21) ◽  
pp. 4301-4314 ◽  
Author(s):  
José-Eduardo Gomes ◽  
Sandra E. Encalada ◽  
Kathryn A. Swan ◽  
Christopher A. Shelton ◽  
J. Clayton Carter ◽  
...  
Keyword(s):  
Cell Fate ◽  
Mitotic Spindle ◽  
Pdz Domain ◽  
Early Embryo ◽  
Embryonic Cell ◽  
Rna Recognition Motif ◽  
Rna Recognition ◽  
Asymmetric Cell Divisions ◽  
C Elegans ◽  
Cell Divisions

C. elegans embryogenesis begins with a stereotyped sequence of asymmetric cell divisions that are largely responsible for establishing the nematode body plan. These early asymmetries are specified after fertilization by the widely conserved, cortically enriched PAR and PKC-3 proteins, which include three kinases and two PDZ domain proteins. During asymmetric cell divisions in the early embryo, centrosome pairs initially are positioned on transverse axes but then rotate to align with the anteroposterior embryonic axis. We show that rotation of the centrosomal/nuclear complex in an embryonic cell called P1 requires a maternally expressed gene we name spn-4. The predicted SPN-4 protein contains a single RNA recognition motif (RRM), and belongs to a small subfamily of RRM proteins that includes one Drosophila and two human family members. Remarkably, in mutant embryos lacking spn-4 function the transversely oriented ‘P1’ mitotic spindle appears to re-specify the axis of cell polarity, and the division remains asymmetric. spn-4 also is required for other developmental processes, including the specification of mesendoderm, the restriction of mesectoderm fate to P1 descendants, and germline quiescence during embryogenesis. We suggest that SPN-4 post-transcriptionally regulates the expression of multiple developmental regulators. Such SPN-4 targets might then act more specifically to generate a subset of the anterior-posterior asymmetries initially specified after fertilization by the more generally required PAR and PKC-3 proteins.

Specification of anterior-posterior differences within the AB lineage in the C. elegans embryo: a polarising induction

Development ◽  
1995 ◽  
Vol 121 (5) ◽  
pp. 1559-1568 ◽  
Author(s):  
H. Hutter ◽  
R. Schnabel
Keyword(s):  
Cell Fate ◽  
Tissue Type ◽  
Cell Stage ◽  
Anterior Portion ◽  
Developmental Potential ◽  
C Elegans ◽  
The Third ◽  
Inductive Signal ◽  
Anterior Posterior ◽  
Lineage Analysis

In a C. elegans embryo the third cleavages of descendants of the anterior blastomere AB of the 2-cell stage create pairs of blastomeres that develop differently. By laser ablation experiments we show that the fates of all the posterior daughters of this division depend on an induction occurring three cleavages before these blastomeres are born. The time of induction precludes a direct effect on cell fate. Alternatively, we suggest that the induction creates a heritable cell polarity which is propagated through several divisions. We suggest a model to demonstrate how a signal could be propagated through several rounds of cell division. An important implication of our observations is that this early induction acts to specify blastomere identity, not tissue type. A detailed lineage analysis revealed that altering the inductive signal alters complex lineage patterns as a whole. The induction described here, together with two inductions described previously can be used to illustrate how the anterior portion of the C. elegans embryo can be successively subdivided into blastomeres with unique developmental potential.

scholarly journals How embryos work: a comparative view of diverse modes of cell fate specification

Development ◽  
1990 ◽  
Vol 108 (3) ◽  
pp. 365-389 ◽  
Author(s):  
E.H. Davidson
Keyword(s):  
Cell Fate ◽  
Spatial Information ◽  
Cell Interaction ◽  
Cell Fate Specification ◽  
Embryonic Axes ◽  
Gastropod Mollusc ◽  
C Elegans ◽  
Molecular Interpretation ◽  
Gene Regulatory ◽  
Set Up

Embryonic processes in the nematode C. elegans, the gastropod mollusc Ilyanassa, the dipteran Drosophila, the echinoid Strongylocentrotus purpuratus, the ascidian Ciona, the anuran Xenopus, the teleost Brachydanio and mouse are compared with respect to a series of parameters such as invariant or variable cleavage, the means by which the embryonic axes are set up, egg anisotropies and reliance on conditional or on autonomous specification processes. A molecular interpretation of these modes of specification of cell fate in the embryo is proposed, in terms of spatial modifications of gene regulatory factors. On this basis, classically defined phenomena such as regulative development and cytoplasmic localization can be interpreted at a mechanistic level, and the enormous differences between different forms of embryogenesis in the Animal Kingdom can be considered within a common mechanistic framework. Differential spatial expression of histospecific genes is considered in terms of the structure of the gene regulatory network that will be required in embryos that utilize cell-cell interaction, autonomous vs conditional specification and maternal spatial information to differing extents. It is concluded that the regulatory architectures according to which the programs of gene expression are organized are special to each form of development, and that common regulatory principles are to be found only at lower levels, such as those at which the control regions of histospecific structural genes operate.

TRA-1A regulates transcription of fog-3, which controls germ cell fate in C. elegans

Development ◽  
2000 ◽  
Vol 127 (14) ◽  
pp. 3119-3129 ◽  
Author(s):  
P. Chen ◽  
R.E. Ellis
Keyword(s):  
Transcriptional Regulation ◽  
Sexual Identity ◽  
Cell Fate ◽  
Zinc Finger ◽  
Germ Cells ◽  
Zinc Finger Protein ◽  
Rt Pcr ◽  
C Elegans ◽  
Finger Protein

In C. elegans, the zinc-finger protein TRA-1A is thought to be the final arbiter of somatic sexual identity. We show that fog-3, which is required for germ cells to become sperm rather than oocytes, is a target of TRA-1A. First, northern analyses and RT-PCR experiments indicate that expression of fog-3 is controlled by tra-1. Second, studies of double mutants show that this control could be direct. Third, the fog-3 promoter contains multiple sites that bind TRA-1A in gel shift assays, and mutations in these sites alter activity of fog-3 in vivo. These results establish fog-3 as one of the first known targets of transcriptional regulation by TRA-1A. Furthermore, they show that tra-1 controls a terminal regulator of sexual fate in germ cells, just as it is thought to do in the soma.

scholarly journals LET-711, the Caenorhabditis elegans NOT1 Ortholog, Is Required for Spindle Positioning and Regulation of Microtubule Length in Embryos

2006 ◽  
Vol 17 (11) ◽  
pp. 4911-4924 ◽  
Author(s):  
Leah R. DeBella ◽  
Adam Hayashi ◽  
Lesilee S. Rose
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Regulation Of Gene Expression ◽  
Early Embryo ◽  
Cell Cortex ◽  
Loss Of Function ◽  
Wild Type ◽  
Spindle Positioning ◽  
C Elegans ◽  
Associated Proteins

Spindle positioning is essential for the segregation of cell fate determinants during asymmetric division, as well as for proper cellular arrangements during development. In Caenorhabditis elegans embryos, spindle positioning depends on interactions between the astral microtubules and the cell cortex. Here we show that let-711 is required for spindle positioning in the early embryo. Strong loss of let-711 function leads to sterility, whereas partial loss of function results in embryos with defects in the centration and rotation movements that position the first mitotic spindle. let-711 mutant embryos have longer microtubules that are more cold-stable than in wild type, a phenotype opposite to the short microtubule phenotype caused by mutations in the C. elegans XMAP215 homolog ZYG-9. Simultaneous reduction of both ZYG-9 and LET-711 can rescue the centration and rotation defects of both single mutants. let-711 mutant embryos also have larger than wild-type centrosomes at which higher levels of ZYG-9 accumulate compared with wild type. Molecular identification of LET-711 shows it to be an ortholog of NOT1, the core component of the CCR4/NOT complex, which plays roles in the negative regulation of gene expression at transcriptional and post-transcriptional levels in yeast, flies, and mammals. We therefore propose that LET-711 inhibits the expression of ZYG-9 and potentially other centrosome-associated proteins, in order to maintain normal centrosome size and microtubule dynamics during early embryonic divisions.

scholarly journals Early C. elegans embryos modulate cell division timing to compensate for, and survive, the discordant conditions of a severe temperature gradient

2020 ◽  
Author(s):  
Eric Terry ◽  
Bilge Birsoy ◽  
David Bothman ◽  
Marin Sigurdson ◽  
Pradeep M. Joshi ◽  
...  
Keyword(s):  
Cell Division ◽  
Temperature Gradient ◽  
Early Embryo ◽  
Cell Stage ◽  
Division Rate ◽  
Cellular Division ◽  
C Elegans ◽  
Average Decrease ◽  
Slow Development ◽  
Steep Temperature Gradient

AbstractDespite a constant barrage of intrinsic and environmental noise, embryogenesis is remarkably reliable, suggesting the existence of systems that ensure faithful execution of this complex process. We report that early C. elegans embryos, which normally show a highly reproducible lineage and cellular geometry, can compensate for deviations imposed by the discordant conditions of a steep temperature gradient generated in a microfluidic device starting at the two-cell stage. Embryos can survive a gradient of up to 7.5°C across the 50-micron axis through at least three rounds of division. This response is orientation-dependent: survival is higher when the normally faster-dividing anterior daughter of the zygote, AB, but not its sister, the posterior P1, is warmer. We find that temperature-dependent cellular division rates in the early embryo can be effectively modeled by a modification of the Arrhenius equation. Further, both cells respond to the gradient by dramatically reducing division rates compared to the predicted rates for the temperature experienced by the cell even though the temperature extremes are well within the range for normal development. This finding suggests that embryos may sense discordance and slow development in response. We found that in the cohort of surviving embryos, the cell on the warmer side at the two-cell stage shows a greater average decrease in expected division rate than that on the cooler side, thereby preserving the normal cellular geometry of the embryo under the discordant conditions. A diminished average slow-down response correlated with lethality, presumably owing to disruption of normal division order and developmental fidelity. Remarkably, some inviable embryos in which the canonical division order was reversed nonetheless proceeded through relatively normal morphogenesis, suggesting a subsequent compensation mechanism independent of cell division control. These findings provide evidence for a previously unrecognized process in C. elegans embryos that may serve to compensate for deviations imposed by aberrant environmental conditions, thereby resulting in a high-fidelity output.

scholarly journals Logic programming to predict cell fate patterns and retrodict genotypes in organogenesis

2014 ◽  
Vol 11 (98) ◽  
pp. 20140245 ◽  
Author(s):  
Benjamin A. Hall ◽  
Ethan Jackson ◽  
Alex Hajnal ◽  
Jasmin Fisher
Keyword(s):  
Cell Fate ◽  
Formal Analysis ◽  
Cell Fate Determination ◽  
Logic Programs ◽  
Vulval Development ◽  
Analysis Techniques ◽  
C Elegans ◽  
Vulval Precursor Cells ◽  
Powerful Approach ◽  
Temporal And Spatial

Caenorhabditis elegans vulval development is a paradigm system for understanding cell differentiation in the process of organogenesis. Through temporal and spatial controls, the fate pattern of six cells is determined by the competition of the LET-23 and the Notch signalling pathways. Modelling cell fate determination in vulval development using state-based models, coupled with formal analysis techniques, has been established as a powerful approach in predicting the outcome of combinations of mutations. However, computing the outcomes of complex and highly concurrent models can become prohibitive. Here, we show how logic programs derived from state machines describing the differentiation of C. elegans vulval precursor cells can increase the speed of prediction by four orders of magnitude relative to previous approaches. Moreover, this increase in speed allows us to infer, or ‘retrodict’, compatible genomes from cell fate patterns. We exploit this technique to predict highly variable cell fate patterns resulting from dig-1 reduced-function mutations and let-23 mosaics. In addition to the new insights offered, we propose our technique as a platform for aiding the design and analysis of experimental data.

The C. elegans homeodomain gene unc-42 regulates chemosensory and glutamate receptor expression

Development ◽  
1999 ◽  
Vol 126 (10) ◽  
pp. 2241-2251 ◽  
Author(s):  
R. Baran ◽  
R. Aronoff ◽  
G. Garriga
Keyword(s):  
Axon Guidance ◽  
Cell Fate ◽  
Glutamate Receptor ◽  
Sensory Neurons ◽  
Motor Neurons ◽  
Neural Circuits ◽  
Receptor Expression ◽  
Homeodomain Protein ◽  
Sensory Stimuli ◽  
C Elegans

Genes that specify cell fate can influence multiple aspects of neuronal differentiation, including axon guidance, target selection and synapse formation. Mutations in the unc-42 gene disrupt axon guidance along the C. elegans ventral nerve cord and cause distinct functional defects in sensory-locomotory neural circuits. Here we show that unc-42 encodes a novel homeodomain protein that specifies the fate of three classes of neurons in the Caenorhabditis elegans nervous system: the ASH polymodal sensory neurons, the AVA, AVD and AVE interneurons that mediate repulsive sensory stimuli to the nematode head and anterior body, and a subset of motor neurons that innervate head and body-wall muscles. unc-42 is required for the expression of cell-surface receptors that are essential for the mature function of these neurons. In mutant animals, the ASH sensory neurons fail to express SRA-6 and SRB-6, putative chemosensory receptors. The AVA, AVD and AVE interneurons and RME and RMD motor neurons of unc-42 mutants similarly fail to express the GLR-1 glutamate receptor. These results show that unc-42 performs an essential role in defining neuron identity and contributes to the establishment of neural circuits in C. elegans by regulating the transcription of glutamate and chemosensory receptor genes.

scholarly journals Transcript accumulation rates in the early C. elegans embryo

2021 ◽  
Author(s):  
Priya Sivaramakrishnan ◽  
Cameron Watkins ◽  
John Isaac Murray
Keyword(s):  
Transcription Factors ◽  
Cell Fate ◽  
Accumulation Rate ◽  
Core Promoter ◽  
High Rate ◽  
Accumulation Rates ◽  
Transcript Accumulation ◽  
Cell Stage ◽  
Cell Fate Decisions ◽  
C Elegans

Dynamic changes in transcription are widespread in the developing embryo, where cell cycles are rapid and cell fate decisions sometimes need to be made quickly, before the next cell division. In the early Caenorhabditis elegans embryo, specification of the intestine relies on high absolute levels of transcription factors that are a part of the gut gene regulatory network. These absolute levels are likely achieved by controlled transcript accumulation rates. However, accumulation rates have not been measured globally in the worm embryo. We used single cell RNA-seq data from the early C. elegans embryo to estimate the accumulation rates of zygotic genes up to the 24-cell stage. We find that rapid transcript accumulation is a characteristic feature of transcription factors across different cell types and lineages. We identified genomic features associated with high transcription rates and core promoter motifs that might drive these rates. For one Very High-rate gene ceh-51, which is required for mesoderm development, we measured the contributions of core promoter elements to rate. We find that each of these motifs contribute modestly to the accumulation rate of ceh-51, suggesting a complex relationship between promoter motifs and gene structure in controlling transcript accumulation rates. These results are a step towards understanding the regulation of transcript accumulation rates during embryonic cell fate specification.

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