The expression of the C. elegans labial-like Hox gene ceh-13 during early embryogenesis relies on cell fate and on anteroposterior cell polarity

Clusters of homeobox-containing HOM-C/hox genes determine the morphology of animal body plans and body parts and are thought to mediate positional information. Here, we describe the onset of embryonic expression of ceh-13, the Caenorhabditis elegans orthologue of the Drosophila labial gene, which is the earliest gene of the C. elegans Hox gene cluster to be activated in C. elegans development. At the beginning of gastrulation, ceh-13 is asymmetrically expressed in posterior daughters of anteroposterior divisions, first in the posterior daughter of the intestinal precursor cell E and then in all posterior daughters of the AB descendants ABxxx. In this paper, we present evidence that supports position-independent activation of ceh-13 during early C. elegans embryogenesis, which integrates cell fate determinants and cell polarity cues. Our findings imply that mechanisms other than cell-extrinsic anteroposterior positional signals play an important role in the activation and regulation of the C. elegans Hox gene ceh-13.

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The beta-catenin homolog BAR-1 and LET-60 Ras coordinately regulate the Hox gene lin-39 during Caenorhabditis elegans vulval development

Development ◽

10.1242/dev.125.18.3667 ◽

1998 ◽

Vol 125 (18) ◽

pp. 3667-3680 ◽

Cited By ~ 39

Author(s):

D.M. Eisenmann ◽

J.N. Maloof ◽

J.S. Simske ◽

C. Kenyon ◽

S.K. Kim

Keyword(s):

Signaling Pathway ◽

Cell Fate ◽

Precursor Cell ◽

Ras Signaling ◽

Beta Catenin ◽

Cell Fates ◽

Vulval Development ◽

Hox Gene ◽

C Elegans ◽

Vulval Precursor Cell

In C. elegans, the epithelial Pn.p cells adopt either a vulval precursor cell fate or fuse with the surrounding hypodermis (the F fate). Our results suggest that a Wnt signal transduced through a pathway involving the beta-catenin homolog BAR-1 controls whether P3.p through P8.p adopt the vulval precursor cell fate. In bar-1 mutants, P3.p through P8.p can adopt F fates instead of vulval precursor cell fates. The Wnt/bar-1 signaling pathway acts by regulating the expression of the Hox gene lin-39, since bar-1 is required for LIN-39 expression and forced lin-39 expression rescues the bar-1 mutant phenotype. LIN-39 activity is also regulated by the anchor cell signal/let-23 receptor tyrosine kinase/let-60 Ras signaling pathway. Our genetic and molecular experiments show that the vulval precursor cells can integrate the input from the BAR-1 and LET-60 Ras signaling pathways by coordinately regulating activity of the common target LIN-39 Hox.

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egl-27 generates anteroposterior patterns of cell fusion in C. elegans by regulating Hox gene expression and Hox protein function

Development ◽

10.1242/dev.126.15.3303 ◽

1999 ◽

Vol 126 (15) ◽

pp. 3303-3312 ◽

Cited By ~ 1

Author(s):

Q. Ch'ng ◽

C. Kenyon

Keyword(s):

Gene Expression ◽

Cell Fusion ◽

Protein Function ◽

Hox Genes ◽

Positional Information ◽

Cell Fates ◽

Hox Proteins ◽

Hox Gene ◽

C Elegans ◽

Hox Protein

Hox genes pattern the fates of the ventral ectodermal Pn.p cells that lie along the anteroposterior (A/P) body axis of C. elegans. In these cells, the Hox genes are expressed in sequential overlapping domains where they control the ability of each Pn.p cell to fuse with the surrounding syncytial epidermis. The activities of Hox proteins are sex-specific in this tissue, resulting in sex-specific patterns of cell fusion: in hermaphrodites, the mid-body cells remain unfused, whereas in males, alternating domains of syncytial and unfused cells develop. We have found that the gene egl-27, which encodes a C. elegans homologue of a chromatin regulatory factor, specifies these patterns by regulating both Hox gene expression and Hox protein function. In egl-27 mutants, the expression domains of Hox genes in these cells are shifted posteriorly, suggesting that egl-27 influences A/P positional information. In addition, egl-27 controls Hox protein function in the Pn.p cells in two ways: in hermaphrodites it inhibits MAB-5 activity, whereas in males it permits a combinatorial interaction between LIN-39 and MAB-5. Thus, by selectively modifying the activities of Hox proteins, egl-27 elaborates a simple Hox expression pattern into complex patterns of cell fates. Taken together, these results implicate egl-27 in the diversification of cell fates along the A/P axis and suggest that chromatin reorganization is necessary for controlling Hox gene expression and Hox protein function.

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

Development ◽

10.1242/dev.128.22.4645 ◽

2001 ◽

Vol 128 (22) ◽

pp. 4645-4656 ◽

Cited By ~ 1

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.

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

Scientific Reports ◽

10.1038/s41598-018-31688-9 ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 2

Author(s):

András Hartmann ◽

Satoshi Okawa ◽

Gaia Zaffaroni ◽

Antonio del Sol

Keyword(s):

Cell Differentiation ◽

Cell Fate ◽

Web Application ◽

Fate Determinants ◽

Cell Fate Determinants

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A Wnt signaling pathway controls hox gene expression and neuroblast migration in C. elegans

Development ◽

10.1242/dev.126.1.37 ◽

1999 ◽

Vol 126 (1) ◽

pp. 37-49 ◽

Cited By ~ 9

Author(s):

J.N. Maloof ◽

J. Whangbo ◽

J.M. Harris ◽

G.D. Jongeward ◽

C. Kenyon

Keyword(s):

Gene Expression ◽

Wnt Signaling ◽

Wnt Pathway ◽

Hox Genes ◽

Wnt Signaling Pathway ◽

Beta Catenin ◽

Hox Gene ◽

C Elegans ◽

Neuroblast Migration ◽

Pathway Gene

The specification of body pattern along the anteroposterior (A/P) body axis is achieved largely by the actions of conserved clusters of Hox genes. Limiting expression of these genes to localized regional domains and controlling the precise patterns of expression within those domains is critically important for normal patterning. Here we report that egl-20, a C. elegans gene required to activate expression of the Hox gene mab-5 in the migratory neuroblast QL, encodes a member of the Wnt family of secreted glycoproteins. We have found that a second Wnt pathway gene, bar-1, which encodes a beta-catenin/Armadillo-like protein, is also required for activation of mab-5 expression in QL. In addition, we describe the gene pry-1, which is required to limit expression of the Hox genes lin-39, mab-5 and egl-5 to their correct local domains. We find that egl-20, pry-1 and bar-1 all function in a linear genetic pathway with conserved Wnt signaling components, suggesting that a conserved Wnt pathway activates expression of mab-5 in the migratory neuroblast QL. Moreover, we find that members of this Wnt signaling system play a major role in both the general and fine-scale control of Hox gene expression in other cell types along the A/P axis.

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The mab-21 gene of Caenorhabditis elegans encodes a novel protein required for choice of alternate cell fates

Development ◽

10.1242/dev.121.11.3615 ◽

1995 ◽

Vol 121 (11) ◽

pp. 3615-3626 ◽

Cited By ~ 9

Author(s):

K.L. Chow ◽

D.H. Hall ◽

S.W. Emmons

Keyword(s):

Cell Fate ◽

Hox Genes ◽

Cell Signalling ◽

Gene Mutations ◽

Genetic Modifiers ◽

Tail Region ◽

Cell Fates ◽

C Elegans ◽

Body Regions ◽

Novel Protein

The gene mab-21, which encodes a novel protein of 386 amino acids, is required for the choice of alternate cell fates by several cells in the C. elegans male tail. Three cells descended from the ray 6 precursor cell adopt fates of anterior homologs, and a fourth, lineally unrelated hypodermal cell is transformed into a neuroblast. The affected cells lie together in the lateral tail epidermis, suggesting that mab-21 acts as part of a short-range pattern-formation mechanism. Each of the changes in cell fate brought about by mab-21 mutants can be interpreted as a posterior-to-anterior homeotic transformation. mab-21 mutant males and hermaphrodites have additional pleiotropic phenotypes affecting movement, body shape and fecundity, indicating that mab-21 has functions outside the tail region of males. We show that the three known alleles of mab-21 are hypomorphs of a new gene. Mosaic analysis revealed that mab-21 acts cell autonomously to specify the properties of the sensory ray, but non-autonomously in the hypodermal versus neuroblast cell fate choice. Presence of cell signalling in the choice of the neuroblast fate was confirmed by cell ablation experiments. Mutations in mab-21 were shown previously to be genetic modifiers of the effects of HOM-C/Hox gene mutations on ray identity specification. The results presented here support the conclusion that mab-21 acts as part of a mechanism required for correct cell fate choice, possibly involving the function of HOM-C/Hox genes in several body regions.

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

Reproduction ◽

10.1530/rep-15-0301 ◽

2016 ◽

Vol 151 (4) ◽

pp. 351-367 ◽

Cited By ~ 9

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.

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

Molecular Biology of the Cell ◽

10.1091/mbc.e07-02-0105 ◽

2007 ◽

Vol 18 (11) ◽

pp. 4470-4482 ◽

Cited By ~ 25

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.

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