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.

scholarly journals Spindle orientation and epidermal morphogenesis

2013 ◽  
Vol 368 (1629) ◽  
pp. 20130016 ◽  
Author(s):  
Anita Kulukian ◽  
Elaine Fuchs
Keyword(s):  
Stem Cells ◽  
Basement Membrane ◽  
Cell Fate ◽  
Mitotic Spindle ◽  
Spindle Orientation ◽  
Asymmetric Cell Divisions ◽  
Daughter Cells ◽  
Cell Divisions ◽  
Molecular Machinery ◽  
Asymmetric Partitioning

Asymmetric cell divisions (ACDs) result in two unequal daughter cells and are a hallmark of stem cells. ACDs can be achieved either by asymmetric partitioning of proteins and organelles or by asymmetric cell fate acquisition due to the microenvironment in which the daughters are placed. Increasing evidence suggests that in the mammalian epidermis, both of these processes occur. During embryonic epidermal development, changes occur in the orientation of the mitotic spindle in relation to the underlying basement membrane. These changes are guided by conserved molecular machinery that is operative in lower eukaryotes and dictates asymmetric partitioning of proteins during cell divisions. That said, the shift in spindle alignment also determines whether a division will be parallel or perpendicular to the basement membrane, and this in turn provides a differential microenvironment for the resulting daughter cells. Here, we review how oriented divisions of progenitors contribute to the development and stratification of the epidermis.

A functional analysis of inscuteable and its roles during Drosophila asymmetric cell divisions

1999 ◽  
Vol 112 (10) ◽  
pp. 1541-1551 ◽  
Author(s):  
M. Tio ◽  
M. Zavortink ◽  
X. Yang ◽  
W. Chia
Keyword(s):  
Cell Fate ◽  
Mitotic Spindle ◽  
Mother Cell ◽  
Apical Cell ◽  
Cell Cortex ◽  
Asymmetric Cell Divisions ◽  
Cell Divisions ◽  
Asymmetric Divisions ◽  
Necessary And Sufficient ◽  
Ganglion Mother Cell

Cellular diversity in the Drosophila central nervous system is generated through a series of asymmetric cell divisions in which one progenitor produces two daughter cells with distinct fates. Asymmetric basal cortical localisation and segregation of the determinant Prospero during neuroblast cell divisions play a crucial role in effecting distinct cell fates for the progeny sibling neuroblast and ganglion mother cell. Similarly asymmetric localisation and segregation of the determinant Numb during ganglion mother cell divisions ensure that the progeny sibling neurons attain distinct fates. The most upstream component identified so far which acts to organise both neuroblast and ganglion mother cell asymmetric divisions is encoded by inscuteable. The Inscuteable protein is itself asymmetrically localised to the apical cell cortex and is required both for the basal localisation of the cell fate determinants during mitosis and for the orientation of the mitotic spindle along the apical/basal axis. Here we define the functional domains of Inscuteable. We show that aa252-578 appear sufficient to effect all aspects of its function, however, the precise requirements for its various functions differ. The region, aa288-497, is necessary and sufficient for apical cortical localisation and for mitotic spindle (re)orientation along the apical/basal axis. A larger region aa288-540 is necessary and sufficient for asymmetric Numb localisation and segregation; however, correct localisation of Miranda and Prospero requires additional sequences from aa540-578. The requirement for the resolution of distinct sibling neuronal fates appears to coincide with the region necessary and sufficient for Numb localisation (aa288-540). Our data suggest that apical localisation of the Inscuteable protein is a necessary prerequisite for all other aspects of its function. Finally, we show that although inscuteable RNA is normally apically localised, RNA localisation is not required for protein localisation or any aspects of inscuteable function.

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.

A sperm-supplied factor required for embryogenesis in C. elegans

Development ◽  
1996 ◽  
Vol 122 (1) ◽  
pp. 391-404 ◽  
Author(s):  
H. Browning ◽  
S. Strome
Keyword(s):  
Mitotic Spindle ◽  
Early Embryo ◽  
Lethal Gene ◽  
Cloning And Sequencing ◽  
Paternal Effect ◽  
C Elegans ◽  
Essential Function ◽  
The Many ◽  
Embryonic Viability ◽  
Novel Protein

The paternal-effect embryonic-lethal gene, spe-11, is required for normal development of early C. elegans embryos. Spe-11 embryos fail to complete meiosis, form a weak eggshell, fail to orient properly the first mitotic spindle, and fail to undergo cytokinesis. Here we report cloning and sequencing of the spe-11 gene, which encodes a novel protein. As predicted by the paternal-effect mutant phenotype, the gene is expressed during spermatogenesis but is not detectable in females undergoing oogenesis, and the protein is present in mature sperm. To investigate whether SPE-11's essential function is during spermatogenesis or whether sperm-delivered SPE-11 functions in the newly fertilized embryo, we engineered animals to supply SPE-11 to the embryo through the oocyte rather than through the sperm. We found that maternal expression is sufficient for embryonic viability. This result demonstrates that SPE-11 is not required during spermatogenesis, and suggests that SPE-11 is a sperm-supplied factor that participates directly in development of the early embryo. In contrast to the many known maternal factors required for embryogenesis, SPE-11 is the first paternally contributed factor to be genetically identified and molecularly characterized.

scholarly journals HIPPO signaling resolves embryonic cell fate conflicts during establishment of pluripotency in vivo

2018 ◽  
Author(s):  
Tristan Frum ◽  
Tayler Murphy ◽  
Amy Ralston
Keyword(s):  
Cell Fate ◽  
Early Embryo ◽  
Embryonic Cell ◽  
Hippo Signaling ◽  
Mammalian Development ◽  
Mouse Early Embryo ◽  
Cell Positioning ◽  
Apical Localization ◽  
Complex Components

AbstractDuring mammalian development, the challenge for the embryo is to override intrinsic cellular plasticity to drive cells to distinct fates. Here, we unveil novel roles for the HIPPO signaling pathway segregates pluripotent and extraembryonic fates by controlling cell positioning as well as expression of Sox2, the first marker of pluripotency in the mouse early embryo. We show that maternal and zygotic YAP1 and WWTR1 repress Sox2 while promoting expression of the trophectoderm gene Cdx2 in parallel. Yet, Sox2 is more sensitive than Cdx2 to Yap1/Wwtr1 dosage, leading cells to a state of conflicted cell fate when YAP1/WWTR1 activity is moderate. Remarkably, HIPPO signaling activity resolves conflicted cell fate by repositioning cells to the interior of the embryo, independent of its role in regulating Sox2 expression. Rather, HIPPO antagonizes apical localization of Par complex components PARD6B and aPKC. Thus, negative feedback between HIPPO and Par complex components ensure robust lineage segregation.

scholarly journals HIPPO signaling resolves embryonic cell fate conflicts during establishment of pluripotency in vivo

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Tristan Frum ◽  
Tayler M Murphy ◽  
Amy Ralston
Keyword(s):  
Cell Fate ◽  
Early Embryo ◽  
Embryonic Cell ◽  
Hippo Signaling ◽  
Mammalian Development ◽  
Sox2 Expression ◽  
Mouse Early Embryo ◽  
Cell Positioning ◽  
Complex Components

During mammalian development, the challenge for the embryo is to override intrinsic cellular plasticity to drive cells to distinct fates. Here, we unveil novel roles for the HIPPO signaling pathway in controlling cell positioning and expression of Sox2, the first marker of pluripotency in the mouse early embryo. We show that maternal and zygotic YAP1 and WWTR1 repress Sox2 while promoting expression of the trophectoderm gene Cdx2 in parallel. Yet, Sox2 is more sensitive than Cdx2 to Yap1/Wwtr1 dosage, leading cells to a state of conflicted cell fate when YAP1/WWTR1 activity is moderate. Remarkably, HIPPO signaling activity resolves conflicted cell fate by repositioning cells to the interior of the embryo, independent of its role in regulating Sox2 expression. Rather, HIPPO antagonizes apical localization of Par complex components PARD6B and aPKC. Thus, negative feedback between HIPPO and Par complex components ensure robust lineage segregation.

scholarly journals Quantitative and dynamic cell polarity tracking in plant cells

2020 ◽  
Author(s):  
Yan Gong ◽  
Rachel Varnau ◽  
Eva-Sophie Wallner ◽  
Dominique C. Bergmann ◽  
Lily S. Cheung
Keyword(s):  
Cell Fate ◽  
Cell Polarity ◽  
Brachypodium Distachyon ◽  
Quantitative Information ◽  
Tissue Level ◽  
Asymmetric Cell Divisions ◽  
Cell Divisions ◽  
Versatile Tool ◽  
Dynamic Cell ◽  
Microscopy Techniques

ABSTRACTQuantitative information on the spatiotemporal distribution of polarized proteins is central for understanding cell-fate determination, yet collecting sufficient data for statistical analysis is difficult to accomplish with manual measurements. Here we present POME, a semi-automated pipeline for the quantification of cell polarity, and demonstrate its application to a variety of developmental contexts. POME analysis reveals that during asymmetric cell divisions in the Arabidopsis thaliana stomatal lineage, polarity proteins BASL and BRXL2 are more asynchronous and less mutually dependent than previously thought. While their interaction is important to maintain their polar localization and recruit other effectors to regulate asymmetric cell divisions, BRXL2 polarization precedes that of BASL and can be initiated in BASL’s absence. Uncoupling of polarization from BASL activity is also seen in Brachypodium distachyon, where we find that the MAPKKK BdYDA1 is segregated and polarized following asymmetric division. Our results demonstrate that POME is a versatile tool, which by itself or combined with tissue-level studies and advanced microscopy techniques can help uncover new mechanisms of cell polarity.

scholarly journals Regulating the regulator: Numb acts upstream of p53 to control mammary stem and progenitor cell

2015 ◽  
Vol 211 (4) ◽  
pp. 737-739 ◽  
Author(s):  
Marisa M. Faraldo ◽  
Marina A. Glukhova
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Cell Expansion ◽  
Progenitor Cell ◽  
Asymmetric Cell Divisions ◽  
Stem Cell Expansion ◽  
Cell Divisions ◽  
Cell Fate Determinant ◽  
Mammary Stem

In this issue, Tosoni et al. (2015. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201505037) report that cell fate determinant and tumor suppressor Numb imposes asymmetric cell divisions in mammary stem cells by regulating p53. Numb thereby restricts mammary stem cell expansion and controls the proliferation and lineage-specific characteristics of their progeny.

Sign in / Sign up

Export Citation Format

Share Document