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 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.

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 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 The Dynamics of P Granule Liquid Droplets Are Regulated by the Caenorhabditis elegans Germline RNA Helicase GLH-1 via Its ATP Hydrolysis Cycle

Genetics ◽  
2020 ◽  
Vol 215 (2) ◽  
pp. 421-434 ◽  
Author(s):  
Wenjun Chen ◽  
Yabing Hu ◽  
Charles F. Lang ◽  
Jordan S. Brown ◽  
Sierra Schwabach ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Rna Binding ◽  
Atp Hydrolysis ◽  
Rna Binding Proteins ◽  
Rna Helicase ◽  
Liquid Droplets ◽  
P Granules ◽  
Link Type ◽  
Show Evidence

P granules are phase-separated liquid droplets that play important roles in the maintenance of germ cell fate in Caenorhabditis elegans. Both the localization and formation of P granules are highly dynamic, but mechanisms that regulate such processes remain poorly understood. Here, we show evidence that the VASA-like germline RNA helicase GLH-1 couples distinct steps of its ATPase hydrolysis cycle to control the formation and disassembly of P granules. In addition, we found that the phenylalanine-glycine-glycine repeats in GLH-1 promote its localization at the perinucleus. Proteomic analyses of the GLH-1 complex with a GLH-1 mutation that interferes with P granule disassembly revealed transient interactions of GLH-1 with several Argonautes and RNA-binding proteins. Finally, we found that defects in recruiting the P granule component PRG-1 to perinuclear foci in the adult germline correlate with the fertility defects observed in various GLH-1 mutants. Together, our results highlight the versatile roles of an RNA helicase in controlling the formation of liquid droplets in space and time.

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.

scholarly journals The Cell Fate Determinant Musashi Is Controlled Through Dynamic Protein:Protein Interactions

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A555-A555
Author(s):  
Katherine Bronson ◽  
Meenakshisundaram Balasubramaniam ◽  
Linda Hardy ◽  
Gwen V Childs ◽  
Melanie C MacNicol ◽  
...  
Keyword(s):  
Cell Fate ◽  
Oocyte Maturation ◽  
Rna Binding ◽  
Mrna Translation ◽  
Hormone Production ◽  
Target Mrna ◽  
Associated Proteins ◽  
Specific Regulation ◽  
Partner Proteins

Abstract The Musashi RNA-binding protein functions as a gatekeeper of cell maturation and plasticity through the control of target mRNA translation. It is understood that Musashi promotes stem cell self-renewal and opposes differentiation. While Musashi is best characterized as a repressor of target mRNA translation, we have shown that Musashi can activate target mRNA translation in a cell context specific manner via regulatory phosphorylation on two evolutionarily conserved C-terminal serine residues. Our recent work has found that Musashi is expressed in pituitary stem cells as well as in differentiated hormone producing cell lineages in the adult pituitary. We hypothesize that Musashi maintains cell fate plasticity in the adult pituitary to allow the gland to modulate hormone production in response to changing organismal needs. Here, we seek to understand the regulation of Musashi function. Both Musashi isoforms (Musashi1 and Musashi2) contain two RNA-recognition motifs (RRMs) that bind to specific sequences in the 3’-UTR of target mRNA transcripts; however, neither isoform has enzymatic properties and thus functions through interactions with other proteins to regulate translational outcomes, but the identity and role of Musashi partner proteins is largely unknown. In this study, we have identified co-associated partner proteins that functionally contribute to Musashi-dependent mRNA translational activation during the maturation of Xenopus oocytes. Using mass spectrometry, we identified 29 co-associated proteins that interact specifically with Musashi1 during oocyte maturation and determined that the Musashi co-associated proteins ePABP, PABP4, LSM14A/B, CELF2, PUM1, ELAV1, ELAV2, and DDX6 attenuated oocyte maturation through individual antisense DNA oligo knockdowns. An assessment of the role of these cofactors in the control of Musashi-dependent target mRNA translation is in progress. In addition to studying co-associated proteins, we have created a computational 3D model of the Musashi1 molecule to assist in our investigation Musashi dimerization. This model has indicated that both Musashi1 dimerization and Musashi1:Musashi2 heterodimerization are energetically favorable, and co-pulldown studies have verified both Musashi1 homo-dimerization and Musashi1:Musashi2 heterodimerization in vivo. Computational modeling of Musashi dimer complexes has also identified the key amino acids necessary for these interactions. The contribution of each co-associated protein’s influence on Musashi-dependent translation, relative to the requirement for Musashi:Musashi dimerization, is expected to provide unparalleled insight into regulation of Musashi action. Moreover, cell type specific regulation of association of Musashi co-factors would directly influence Musashi target mRNA translation in oocyte maturation and during pituitary cell plasticity.

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