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

Development ◽  
1995 ◽  
Vol 121 (11) ◽  
pp. 3615-3626 ◽  
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.

scholarly journals REF-1, a protein with two bHLH domains, alters the pattern of cell fusion in C. elegans by regulating Hox protein activity

Development ◽  
2001 ◽  
Vol 128 (10) ◽  
pp. 1793-1804 ◽  
Author(s):  
S. Alper ◽  
C. Kenyon
Keyword(s):  
Cell Fate ◽  
Cell Fusion ◽  
Hox Genes ◽  
Body Axis ◽  
Body Region ◽  
Protein Activity ◽  
Cell Fate Decisions ◽  
C Elegans ◽  
Helix Loop Helix ◽  
Body Regions

Hox genes control the choice of cell fates along the anteroposterior (AP) body axis of many organisms. In C. elegans, two Hox genes, lin-39 and mab-5, control the cell fusion decision of the 12 ventrally located Pn.p cells. Specific Pn.p cells fuse with an epidermal syncytium, hyp7, in a sexually dimorphic pattern. In hermaphrodites, Pn.p cells in the mid-body region remain unfused whereas in males, Pn.p cells adopt an alternating pattern of syncytial and unfused fates. The complexity of these fusion patterns arises because the activities of these two Hox proteins are regulated in a sex-specific manner. MAB-5 activity is inhibited in hermaphrodite Pn.p cells and thus MAB-5 normally only affects the male Pn.p fusion pattern. Here we identify a gene, ref-1, that regulates the hermaphrodite Pn.p cell fusion pattern largely by regulating MAB-5 activity in these cells. Mutation of ref-1 also affects the fate of other epidermal cells in distinct AP body regions. ref-1 encodes a protein with two basic helix-loop-helix domains distantly related to those of the hairy/Enhancer of split family. ref-1, and another hairy homolog, lin-22, regulate similar cell fate decisions in different body regions along the C. elegans AP body axis.

scholarly journals Transcriptional Regulation of Dental Epithelial Cell Fate

2020 ◽  
Vol 21 (23) ◽  
pp. 8952
Author(s):  
Keigo Yoshizaki ◽  
Satoshi Fukumoto ◽  
Daniel D. Bikle ◽  
Yuko Oda
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Gene Mutations ◽  
Dental Enamel ◽  
The Body ◽  
Epithelial Stem Cells ◽  
Cell Fates ◽  
Chromatin Regulators ◽  
Dental Epithelium ◽  
Potential Tool

Dental enamel is hardest tissue in the body and is produced by dental epithelial cells residing in the tooth. Their cell fates are tightly controlled by transcriptional programs that are facilitated by fate determining transcription factors and chromatin regulators. Understanding the transcriptional program controlling dental cell fate is critical for our efforts to build and repair teeth. In this review, we describe the current understanding of these regulators essential for regeneration of dental epithelial stem cells and progeny, which are identified through transgenic mouse models. We first describe the development and morphogenesis of mouse dental epithelium in which different subpopulations of epithelia such as ameloblasts contribute to enamel formation. Then, we describe the function of critical factors in stem cells or progeny to drive enamel lineages. We also show that gene mutations of these factors are associated with dental anomalies in craniofacial diseases in humans. We also describe the function of the master regulators to govern dental lineages, in which the genetic removal of each factor switches dental cell fate to that generating hair. The distinct and related mechanisms responsible for the lineage plasticity are discussed. This knowledge will lead us to develop a potential tool for bioengineering new teeth.

scholarly journals PAG-3, a Zn-finger transcription factor, determines neuroblast fate in C. elegans

Development ◽  
2002 ◽  
Vol 129 (7) ◽  
pp. 1763-1774 ◽  
Author(s):  
Scott Cameron ◽  
Scott G. Clark ◽  
Joan B. McDermott ◽  
Eric Aamodt ◽  
H. Robert Horvitz
Keyword(s):  
Transcription Factor ◽  
Cell Fate ◽  
Daughter Cell ◽  
Cell Lineage ◽  
Blast Cell ◽  
Cell Fates ◽  
Zinc Finger Transcription Factor ◽  
C Elegans ◽  
Mother Cells

During Caenorhabditis elegans development, the patterns of cell divisions, cell fates and programmed cell deaths are reproducible from animal to animal. In a search for mutants with abnormal patterns of programmed cell deaths in the ventral nerve cord, we identified mutations in the gene pag-3, which encodes a zinc-finger transcription factor similar to the mammalian Gfi-1 and Drosophila Senseless proteins. In pag-3 mutants, specific neuroblasts express the pattern of divisions normally associated with their mother cells, producing with each reiteration an abnormal anterior daughter neuroblast and an extra posterior daughter cell that either terminally differentiates or undergoes programmed cell death, which accounts for the extra cell corpses seen in pag-3 mutants. In addition, some neurons do not adopt their normal fates in pag-3 mutants. The phenotype of pag-3 mutants and the expression pattern of the PAG-3 protein suggest that in some lineages pag-3 couples the determination of neuroblast cell fate to subsequent neuronal differentiation. We propose that pag-3 counterparts in other organisms determine blast cell identity and for this reason may lead to cell lineage defects and cell proliferation when mutated.

pos-1 encodes a cytoplasmic zinc-finger protein essential for germline specification in C. elegans

Development ◽  
1999 ◽  
Vol 126 (1) ◽  
pp. 1-11 ◽  
Author(s):  
H. Tabara ◽  
R.J. Hill ◽  
C.C. Mello ◽  
J.R. Priess ◽  
Y. Kohara
Keyword(s):  
Germ Cell ◽  
Zinc Finger Protein ◽  
Early Embryogenesis ◽  
Cell Fates ◽  
C Elegans ◽  
Lethal Mutations ◽  
Finger Protein ◽  
Asymmetric Divisions ◽  
Maternal Mrnas ◽  
Novel Protein

Germ cells arise during early C. elegans embryogenesis from an invariant sequence of asymmetric divisions that separate germ cell precursors from somatic precursors. We show that maternal-effect lethal mutations in the gene pos-1 cause germ cell precursors to inappropriately adopt somatic cell fates. During early embryogenesis, pos-1 mRNA and POS-1 protein are present predominantly in the germ precursors. POS-1 is a novel protein with two copies of a CCCH finger motif previously described in the germline proteins PIE-1 and MEX-1 in C. elegans, and in the mammalian TIS11/Nup475/TTP protein. However, mutations in pos-1 cause several defects in the development of the germline blastomeres that are distinct from those caused by mutations in pie-1 or mex-1. The earliest defect detected in pos-1 mutants is the failure to express APX-1 protein from maternally provided apx-1 mRNA, suggesting that POS-1 may have an important role in regulating the expression of maternal mRNAs in germline blastomeres.

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

Development ◽  
1998 ◽  
Vol 125 (18) ◽  
pp. 3667-3680 ◽  
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.

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

Development ◽  
1999 ◽  
Vol 126 (15) ◽  
pp. 3303-3312 ◽  
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.

scholarly journals The Signaling Network Controlling C. elegans Vulval Cell Fate Patterning

2018 ◽  
Vol 6 (4) ◽  
pp. 30 ◽  
Author(s):  
Hanna Shin ◽  
David Reiner
Keyword(s):  
Cell Fate ◽  
Signaling Network ◽  
Signaling Cascades ◽  
Cell Fates ◽  
C Elegans ◽  
Differentiated Cells ◽  
Vulval Precursor Cells ◽  
Cell Patterns ◽  
History Of ◽  
Anchor Cell

EGF, emitted by the Anchor Cell, patterns six equipotent C. elegans vulval precursor cells to assume a precise array of three cell fates with high fidelity. A group of core and modulatory signaling cascades forms a signaling network that demonstrates plasticity during the transition from naïve to terminally differentiated cells. In this review, we summarize the history of classical developmental manipulations and molecular genetics experiments that led to our understanding of the signals governing this process, and discuss principles of signal transduction and developmental biology that have emerged from these studies.

scholarly journals Regulation of nuclear-cytoplasmic partitioning by the lin-28-lin-46 pathway reinforces microRNA repression of HBL-1 to confer robust cell-fate progression in C. elegans

2019 ◽  
Author(s):  
Orkan Ilbay ◽  
Victor Ambros
Keyword(s):  
Cell Fate ◽  
Translational Regulation ◽  
Rna Binding ◽  
Nuclear Accumulation ◽  
Synthesis Rate ◽  
Microrna Target ◽  
Cell Fates ◽  
Down Regulation ◽  
C Elegans ◽  
Necessary And Sufficient

AbstractMicroRNAs target complementary mRNAs for degradation or translational repression, reducing or preventing protein synthesis. In C. elegans, the transcription factor HBL-1 (Hunchback-like 1) promotes early larval (L2) stage cell-fate, and the let-7-family microRNAs temporally down-regulate HBL-1 to enable the L2-to-L3 cell-fate progression. In parallel to let-7-family microRNAs, the conserved RNA binding protein LIN-28 and its downstream gene lin-46, also act upstream of HBL-1 in regulating the L2-to-L3 cell-fate progression. The molecular function of LIN-46, and how the lin-28-lin-46 pathway regulates HBL-1, are not understood. Here, we report that the regulation of HBL-1 by the lin-28-lin-46 pathway is independent of the let-7/lin-4 microRNA complementary sites (LCSs) in the hbl-1 3’UTR, and involves a stage-specific post-translational regulation of HBL-1 nuclear accumulation. We find that LIN-46 is necessary and sufficient to prevent nuclear accumulation of HBL-1. Our results illuminate that the robust progression from L2 to L3 cell-fates depends on the combination of two distinct modes of HBL-1 down-regulation: decreased synthesis of HBL-1 via let-7-family microRNA activity, and decreased nuclear accumulation of HBL-1 via action of the lin-28-lin-46 pathway. Like HBL-1, many microRNA targets are transcription factors (TFs); and cooperation between regulation of nuclear accumulation and microRNA-mediated control of synthesis rate may be required to increase the precision of or confer robustness to down-regulation of these microRNA target TFs, which can be critical to achieve the optimal phenotypes.

scholarly journals Cell fate patterning during C. elegans vulval development

Development ◽  
1993 ◽  
Vol 119 (Supplement) ◽  
pp. 9-18 ◽  
Author(s):  
Russell J. Hill ◽  
Paul W. Sternberg
Keyword(s):  
Cell Fate ◽  
Short Range ◽  
Precursor Cells ◽  
Cell Fates ◽  
Vulval Development ◽  
C Elegans ◽  
Vulval Precursor Cells ◽  
Combined Action ◽  
Anchor Cell ◽  
Inductive Signal

Precursor cells of the vulva of the C. elegans hermaphrodite choose between two vulval cell fates (1° and 2°) and a non-vulval epidermal fate (3°) in response to three intercellular signals. An inductive signal produced by the anchor cell induces the vulval precursors to assume the 1° and 2° vulval fates. This inductive signal is an EGF-like growth factor encoded by the gene lin-3. An inhibitory signal mediated by lin-15, and which may originate from the surrounding epidermis, prevents the vulval precursors from assuming vulval fates in the absence of the inductive signal. A short range lateral signal, which acts through the gene lin-12, regulates the pattern of 1° and 2° fates assumed by the induced vulval precursors. The combined action of the three signals precisely directs the six vulval precursors to adopt a 3° 3° 2° 1° 2 ° 3° pattern of fates. The amount of inductive signal produced by the anchor cell appears to determine the number or vulval precursors that assume vulval fates. The three induced vulval precursors most proximal to the anchor cell are proposed to adopt the 2° 1° 2° pattern of fates in response to a gradient of the inductive signal and also in response to lateral signalling that inhibits adjacent vulval precursor cells from both assuming the 1° fate.

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

Development ◽  
1997 ◽  
Vol 124 (21) ◽  
pp. 4193-4200 ◽  
Author(s):  
C. Wittmann ◽  
O. Bossinger ◽  
B. Goldstein ◽  
M. Fleischmann ◽  
R. Kohler ◽  
...  
Keyword(s):  
Cell Fate ◽  
Cell Polarity ◽  
Hox Genes ◽  
Positional Information ◽  
Precursor Cell ◽  
Body Parts ◽  
Hox Gene ◽  
C Elegans ◽  
Fate Determinants ◽  
Cell Fate Determinants

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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