scholarly journals PAR-3 and PAR-1 Inhibit LET-99 Localization to Generate a Cortical Band Important for Spindle Positioning in Caenorhabditis elegans Embryos

2007 ◽  
Vol 18 (11) ◽  
pp. 4470-4482 ◽  
Author(s):  
Jui-Ching Wu ◽  
Lesilee S. Rose
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Protein Signaling ◽  
Posterior Cortex ◽  
Par Proteins ◽  
Anterior Cortex ◽  
Spindle Positioning ◽  
High Let ◽  
Fate Determinants ◽  
Cell Fate Determinants

The conserved PAR proteins are localized in asymmetric cortical domains and are required for the polarized localization of cell fate determinants in many organisms. In Caenorhabditis elegans embryos, LET-99 and G protein signaling act downstream of the PARs to regulate spindle positioning and ensure asymmetric division. PAR-3 and PAR-2 localize LET-99 to a posterior cortical band through an unknown mechanism. Here we report that LET-99 asymmetry depends on cortically localized PAR-1 and PAR-4 but not on cytoplasmic polarity effectors. In par-1 and par-4 embryos, LET-99 accumulates at the entire posterior cortex, but remains at low levels at the anterior cortex occupied by PAR-3. Further, PAR-3 and PAR-1 have graded cortical distributions with the highest levels at the anterior and posterior poles, respectively, and the lowest levels of these proteins correlate with high LET-99 accumulation. These results suggest that PAR-3 and PAR-1 inhibit the localization of LET-99 to generate a band pattern. In addition, PAR-1 kinase activity is required for the inhibition of LET-99 localization, and PAR-1 associates with LET-99. Finally, examination of par-1 embryos suggests that the banded pattern of LET-99 is critical for normal posterior spindle displacement and to prevent spindle misorientation caused by cell shape constraints.

scholarly journals The APC/CFZY–1/Cdc20 Complex Coordinates With OMA-1 to Regulate the Oocyte-to-Embryo Transition in Caenorhabditis elegans

2021 ◽  
Vol 9 ◽  
Author(s):  
Yabing Hu ◽  
Xuewen Hu ◽  
Dongchen Li ◽  
Zhenzhen Du ◽  
Kun Shi ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Zinc Finger ◽  
Oocyte Maturation ◽  
Rna Binding ◽  
Gain Of Function ◽  
Ccch Zinc Finger ◽  
C Complex ◽  
Fate Determinants ◽  
Cell Fate Determinants

During oocyte maturation and the oocyte-to-embryo transition, key developmental regulators such as RNA-binding proteins coordinate translation of particular messenger RNA (mRNAs) and related developmental processes by binding to their cognate maternal mRNAs. In the nematode Caenorhabditis elegans, these processes are regulated by a set of CCCH zinc finger proteins. Oocyte maturation defective-1 (OMA-1) and OMA-2 are two functionally redundant CCCH zinc finger proteins that turnover rapidly during the first embryonic cell division. These turnovers are required for proper transition from oogenesis to embryogenesis. A gain-of-function mutant of OMA-1, oma-1(zu405), stabilizes and delays degradation of OMA-1, resulting in delayed turnover and mis-segregation of other cell fate determinants, which eventually causes embryonic lethality. We performed a large-scale forward genetic screen to identify suppressors of the oma-1(zu405) mutant. We show here that multiple alleles affecting functions of various anaphase promoting complex/cyclosome (APC/C) subunits, including MAT-1, MAT-2, MAT-3, EMB-30, and FZY-1, suppress the gain-of-function mutant of OMA-1. Transcriptome analysis suggested that overall transcription in early embryos occurred after introducing mutations in APC/C genes into the oma-1(zu405) mutant. Mutations in APC/C genes prevent OMA-1 enrichment in P granules and correct delayed degradation of downstream cell fate determinants including pharynx and intestine in excess-1 (PIE-1), posterior segregation-1 (POS-1), muscle excess-3 (MEX-3), and maternal effect germ-cell defective-1 (MEG-1). We demonstrated that only the activator FZY-1, but not FZR-1, is incorporated in the APC/C complex to regulate the oocyte-to-embryo transition. Our findings suggested a genetic relationship linking the APC/C complex and OMA-1, and support a model in which the APC/C complex promotes P granule accumulation and modifies RNA binding of OMA-1 to regulate the oocyte-to-embryo transition process.

scholarly journals The polarity-induced force imbalance inCaenorhabditis elegansembryos is caused by asymmetric binding rates of dynein to the cortex

2018 ◽  
Vol 29 (26) ◽  
pp. 3093-3104 ◽  
Author(s):  
Ruddi Rodriguez-Garcia ◽  
Laurent Chesneau ◽  
Sylvain Pastezeur ◽  
Julien Roul ◽  
Marc Tramier ◽  
...  
Keyword(s):  
Cell Fate ◽  
Asymmetric Cell Division ◽  
Molecular Motor ◽  
Dependent Manner ◽  
Mitotic Progression ◽  
Posterior Cortex ◽  
Antibody Staining ◽  
Pulling Forces ◽  
Fate Determinants ◽  
Cell Fate Determinants

During asymmetric cell division, the molecular motor dynein generates cortical pulling forces that position the spindle to reflect polarity and adequately distribute cell fate determinants. In Caenorhabditis elegans embryos, despite a measured anteroposterior force imbalance, antibody staining failed to reveal dynein enrichment at the posterior cortex, suggesting a transient localization there. Dynein accumulates at the microtubule plus ends, in an EBP-2EB–dependent manner. This accumulation, although not transporting dynein, contributes modestly to cortical forces. Most dyneins may instead diffuse to the cortex. Tracking of cortical dynein revealed two motions: one directed and the other diffusive-like, corresponding to force-generating events. Surprisingly, while dynein is not polarized at the plus ends or in the cytoplasm, diffusive-like tracks were more frequently found at the embryo posterior tip, where the forces are higher. This asymmetry depends on GPR-1/2LGNand LIN-5NuMA, which are enriched there. In csnk-1(RNAi) embryos, the inverse distribution of these proteins coincides with an increased frequency of diffusive-like tracks anteriorly. Importantly, dynein cortical residence time is always symmetric. We propose that the dynein-binding rate at the posterior cortex is increased, causing the polarity-reflecting force imbalance. This mechanism of control supplements the regulation of mitotic progression through the nonpolarized dynein detachment rate.

The Caenorhabditis elegans polarity gene ooc-5 encodes a Torsin-related protein of the AAA ATPase superfamily

Development ◽  
2001 ◽  
Vol 128 (22) ◽  
pp. 4645-4656 ◽  
Author(s):  
Stephen E. Basham ◽  
Lesilee S. Rose
Keyword(s):  
Cell Fate ◽  
Protein Complexes ◽  
Sequence Similarity ◽  
Normal Function ◽  
Par Proteins ◽  
Torsion Dystonia ◽  
Aaa Atpase ◽  
C Elegans ◽  
Fate Determinants ◽  
Cell Fate Determinants

The PAR proteins are required for polarity and asymmetric localization of cell fate determinants in C. elegans embryos. In addition, several of the PAR proteins are conserved and localized asymmetrically in polarized cells in Drosophila, Xenopus and mammals. We have previously shown that ooc-5 and ooc-3 mutations result in defects in spindle orientation and polarity in early C. elegans embryos. In particular, mutations in these genes affect the re-establishment of PAR protein asymmetry in the P1 cell of two-cell embryos. We now report that ooc-5 encodes a putative ATPase of the Clp/Hsp100 and AAA superfamilies of proteins, with highest sequence similarity to Torsin proteins; the gene for human Torsin A is mutated in individuals with early-onset torsion dystonia, a neuromuscular disease. Although Clp/Hsp100 and AAA family proteins have roles in diverse cellular activities, many are involved in the assembly or disassembly of proteins or protein complexes; thus, OOC-5 may function as a chaperone. OOC-5 protein co-localizes with a marker of the endoplasmic reticulum in all blastomeres of the early C. elegans embryo, in a pattern indistinguishable from that of OOC-3 protein. Furthermore, OOC-5 localization depends on the normal function of the ooc-3 gene. These results suggest that OOC-3 and OOC-5 function in the secretion of proteins required for the localization of PAR proteins in the P1 cell, and may have implications for the study of torsion dystonia.

scholarly journals Asymmetric enrichment of PIE-1 in the Caenorhabditis elegans zygote mediated by binary counterdiffusion

2009 ◽  
Vol 184 (4) ◽  
pp. 473-479 ◽  
Author(s):  
Brian R. Daniels ◽  
Edward M. Perkins ◽  
Terrence M. Dobrowsky ◽  
Sean X. Sun ◽  
Denis Wirtz
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Heterogeneous Reaction ◽  
Reaction Diffusion ◽  
Developmental Potential ◽  
Daughter Cells ◽  
Reaction Diffusion Model ◽  
Fate Determinants ◽  
Cell Fate Determinants ◽  
Enrichment Process

To generate cellular diversity in developing organisms while simultaneously maintaining the developmental potential of the germline, germ cells must be able to preferentially endow germline daughter cells with a cytoplasmic portion containing specialized cell fate determinants not inherited by somatic cells. In Caenorhabditis elegans, germline inheritance of the protein PIE-1 is accomplished by first asymmetrically localizing the protein to the germplasm before cleavage and subsequently degrading residual levels of the protein in the somatic cytoplasm after cleavage. Despite its critical involvement in cell fate determination, the enrichment of germline determinants remains poorly understood. Here, combining live-cell fluorescence methods and kinetic modeling, we demonstrate that the enrichment process does not involve protein immobilization, intracellular compartmentalization, or localized protein degradation. Instead, our results support a heterogeneous reaction/diffusion model for PIE-1 enrichment in which the diffusion coefficient of PIE-1 is reversibly reduced in the posterior, resulting in a stable protein gradient across the zygote at steady state.

scholarly journals SeesawPred: A Web Application for Predicting Cell-fate Determinants in Cell Differentiation

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
András Hartmann ◽  
Satoshi Okawa ◽  
Gaia Zaffaroni ◽  
Antonio del Sol
Keyword(s):  
Cell Differentiation ◽  
Cell Fate ◽  
Web Application ◽  
Fate Determinants ◽  
Cell Fate Determinants

scholarly journals Unequal distribution of 16S mtrRNA at the 2-cell stage regulates cell lineage allocations in mouse embryos

Reproduction ◽  
2016 ◽  
Vol 151 (4) ◽  
pp. 351-367 ◽  
Author(s):  
Zhuxia Zheng ◽  
Hongmei Li ◽  
Qinfen Zhang ◽  
Lele Yang ◽  
Huayu Qi
Keyword(s):  
Cell Fate ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Cell Lineage ◽  
Early Embryogenesis ◽  
Embryonic Cells ◽  
Cell Stage ◽  
Unequal Distribution ◽  
Fate Determinants ◽  
Cell Fate Determinants

Cell lineage determination during early embryogenesis has profound effects on adult animal development. Pre-patterning of embryos, such as that of Drosophila and Caenorhabditis elegans, is driven by asymmetrically localized maternal or zygotic factors, including mRNA species and RNA binding proteins. However, it is not clear how mammalian early embryogenesis is regulated and what the early cell fate determinants are. Here we show that, in mouse, mitochondrial ribosomal RNAs (mtrRNAs) are differentially distributed between 2-cell sister blastomeres. This distribution pattern is not related to the overall quantity or activity of mitochondria which appears equal between 2-cell sister blastomeres. Like in lower species, 16S mtrRNA is found to localize in the cytoplasm outside of mitochondria in mouse 2-cell embryos. Alterations of 16S mtrRNA levels in one of the 2-cell sister blastomere via microinjection of either sense or anti-sense RNAs drive its progeny into different cell lineages in blastocyst. These results indicate that mtrRNAs are differentially distributed among embryonic cells at the beginning of embryogenesis in mouse and they are functionally involved in the regulation of cell lineage allocations in blastocyst, suggesting an underlying molecular mechanism that regulates pre-implantation embryogenesis in mouse.

The endocytic adaptor Numb regulates thymus size by modulating pre-TCR signaling during asymmetric division

Blood ◽  
2010 ◽  
Vol 116 (10) ◽  
pp. 1705-1714 ◽  
Author(s):  
Rocio Aguado ◽  
Nadia Martin-Blanco ◽  
Michael Caraballo ◽  
Matilde Canelles
Keyword(s):  
Cell Fate ◽  
Asymmetric Division ◽  
Cell Receptor ◽  
Dominant Negative ◽  
Thymocyte Development ◽  
Tcr Signaling ◽  
Daughter Cells ◽  
Fate Determinants ◽  
Cell Fate Determinants

Abstract Stem cells must proliferate and differentiate to generate the lineages that shape mature organs; understanding these 2 processes and their interaction is one of the central themes in current biomedicine. An intriguing aspect is asymmetric division, by which 2 daughter cells with different fates are generated. Several cell fate determinants participate in asymmetric division, with the endocytic adaptor Numb as the best-known example. Here, we have explored the role of asymmetric division in thymocyte development, visualizing the differential segregation of Numb and pre-TCR in thymic precursors. Analysis of mice where Numb had been inhibited by expressing a dominant negative revealed enhanced pre–T-cell receptor (TCR) signaling and a smaller thymus. Conversely, Numb overexpression resulted in loss of asymmetric division and a larger thymus. The conclusion is that Numb determines the levels of pre-TCR signaling in dividing thymocytes and, ultimately, the size of the pool from which mature T lymphocytes are selected.

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