scholarly journals let-7 controls the transition to adulthood by releasing select transcriptional regulators from repression by LIN41

2018 ◽  
Author(s):  
Florian Aeschimann ◽  
Anca Neagu ◽  
Magdalene Rausch ◽  
Helge Großhans
Keyword(s):  
Transition To Adulthood ◽  
Progenitor Cell ◽  
Temporal Patterning ◽  
Cell Fates ◽  
C Elegans ◽  
Regulatory Module ◽  
Single Target ◽  
Dm Domain ◽  
Multicellular Organisms ◽  
Post Transcriptional Regulation

ABSTRACTDevelopment of multicellular organisms relies on faithful temporal control of cell fates. In Caenorhabditis elegans, the heterochronic pathway governs temporal patterning of somatic cells. This function may be phylogenetically conserved as several heterochronic genes have mammalian orthologues, and as the heterochronic let-7 miRNA and its regulator LIN28 appear to time the onset of puberty in mice and humans. Here, we have investigated how let-7 promotes the transition to adulthood in C. elegans. We find that let-7 controls each of three relevant processes, namely male and female sexual organ morphogenesis as well as changes in skin progenitor cell fates, through the same single target, lin-41. LIN41 in turn silences two pairs of targets post-transcriptionally, by binding and silencing their mRNAs. The EGR-type transcription factor LIN-29a and its co-factor, the NAB1/2 orthologous MAB-10, mediate control of progenitor cell fates and vulval integrity. By contrast, male tail development depends on regulation of the DM domain-containing transcription factors DMD-3 and MAB-3. Our results provide mechanistic insight into an exemplary temporal patterning pathway, demonstrate that let-7 – LIN41 function as a versatile regulatory module that can be connected to different outputs, and reveal how several levels of post-transcriptional regulation ultimately achieve effects through controlling transcriptional outputs.

scholarly journals let-7 coordinates the transition to adulthood through a single primary and four secondary targets

2019 ◽  
Vol 2 (2) ◽  
pp. e201900335 ◽  
Author(s):  
Florian Aeschimann ◽  
Anca Neagu ◽  
Magdalene Rausch ◽  
Helge Großhans
Keyword(s):  
Transition To Adulthood ◽  
Progenitor Cell ◽  
Rna Binding ◽  
Linear Chain ◽  
Transcriptional Regulators ◽  
Cell Fates ◽  
Sexual Organ ◽  
Single Target ◽  
Small Set ◽  
And Function

The juvenile-to-adult (J/A) transition, or puberty, is a period of extensive changes of animal body morphology and function. The onset of puberty is genetically controlled, and the let-7 miRNA temporally regulates J/A transition events in nematodes and mammals. Here, we uncover the targets and downstream pathways through which Caenorhabditis elegans let-7 controls male and female sexual organ morphogenesis and skin progenitor cell fates. We find that let-7 directs all three processes by silencing a single target, the post-transcriptional regulator lin-41. In turn, the RNA-binding protein LIN41/TRIM71 regulates these processes by silencing only four target mRNAs. Thus, by silencing LIN41, let-7 activates LIN-29a and MAB-10 (an early growth response-type transcription factor and its NAB1/2-orthologous cofactor, respectively) to terminate progenitor cell self-renewal and to promote vulval integrity. By contrast, let-7 promotes development of the male sexual organ by up-regulating DMD-3 and MAB-3, two Doublesex/MAB-3 domain–containing transcription factors. Our results provide mechanistic insight into how a linear chain of post-transcriptional regulators diverges in the control of a small set of transcriptional regulators to achieve a coordinated J/A transition.

scholarly journals The secreted endoribonuclease ENDU-2 from the soma protects germline immortality in C. elegans

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wenjing Qi ◽  
Erika D. V. Gromoff ◽  
Fan Xu ◽  
Qian Zhao ◽  
Wei Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Small Rnas ◽  
C Elegans ◽  
Cleavage Activity ◽  
Response To Temperature ◽  
Multicellular Organisms ◽  
Cell Immortality ◽  
Mature Mrnas ◽  
Endoribonuclease Activity

AbstractMulticellular organisms coordinate tissue specific responses to environmental information via both cell-autonomous and non-autonomous mechanisms. In addition to secreted ligands, recent reports implicated release of small RNAs in regulating gene expression across tissue boundaries. Here, we show that the conserved poly-U specific endoribonuclease ENDU-2 in C. elegans is secreted from the soma and taken-up by the germline to ensure germline immortality at elevated temperature. ENDU-2 binds to mature mRNAs and negatively regulates mRNA abundance both in the soma and the germline. While ENDU-2 promotes RNA decay in the soma directly via its endoribonuclease activity, ENDU-2 prevents misexpression of soma-specific genes in the germline and preserves germline immortality independent of its RNA-cleavage activity. In summary, our results suggest that the secreted RNase ENDU-2 regulates gene expression across tissue boundaries in response to temperature alterations and contributes to maintenance of stem cell immortality, probably via retaining a stem cell specific program of gene expression.

Context-specific regulation of lysosomal lipolysis through network-level diverting of transcription factor interactions

2021 ◽  
Vol 118 (41) ◽  
pp. e2104832118
Author(s):  
Vinod K. Mony ◽  
Anna Drangowska-Way ◽  
Reka Albert ◽  
Emma Harrison ◽  
Abbas Ghaddar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Target Gene ◽  
Specific Nature ◽  
C Elegans ◽  
Functional Interactions ◽  
Genetic Epistasis ◽  
Specific Regulation ◽  
Context Specific ◽  
Factor Interactions ◽  
Multicellular Organisms

Plasticity in multicellular organisms involves signaling pathways converting contexts—either natural environmental challenges or laboratory perturbations—into context-specific changes in gene expression. Congruently, the interactions between the signaling molecules and transcription factors (TF) regulating these responses are also context specific. However, when a target gene responds across contexts, the upstream TF identified in one context is often inferred to regulate it across contexts. Reconciling these stable TF–target gene pair inferences with the context-specific nature of homeostatic responses is therefore needed. The induction of the Caenorhabditis elegans genes lipl-3 and lipl-4 is observed in many genetic contexts and is essential to survival during fasting. We find DAF-16/FOXO mediating lipl-4 induction in all contexts tested; hence, lipl-4 regulation seems context independent and compatible with across-context inferences. In contrast, DAF-16–mediated regulation of lipl-3 is context specific. DAF-16 reduces the induction of lipl-3 during fasting, yet it promotes it during oxidative stress. Through discrete dynamic modeling and genetic epistasis, we define that DAF-16 represses HLH-30/TFEB—the main TF activating lipl-3 during fasting. Contrastingly, DAF-16 activates the stress-responsive TF HSF-1 during oxidative stress, which promotes C. elegans survival through induction of lipl-3. Furthermore, the TF MXL-3 contributes to the dominance of HSF-1 at the expense of HLH-30 during oxidative stress but not during fasting. This study shows how context-specific diverting of functional interactions within a molecular network allows cells to specifically respond to a large number of contexts with a limited number of molecular players, a mode of transcriptional regulation we name “contextualized transcription.”

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.

Patterning of the C. elegans 1 degrees vulval lineage by RAS and Wnt pathways

Development ◽  
2000 ◽  
Vol 127 (23) ◽  
pp. 5047-5058 ◽  
Author(s):  
M. Wang ◽  
P.W. Sternberg
Keyword(s):  
Short Range ◽  
Precursor Cell ◽  
Ras Signaling ◽  
Cell Fates ◽  
C Elegans ◽  
Asymmetric Divisions ◽  
Anchor Cell ◽  
Wnt Pathways ◽  
Vulval Precursor Cell ◽  
Proper Orientation

In C. elegans, the descendants of the 1 degrees vulval precursor cell (VPC) establish a fixed spatial pattern of two different cell fates: E-F-F-E. The two inner granddaughters attach to the somatic gonadal anchor cell (AC) and generate four vulF cells, while the two outer granddaughters produce four vulE progeny. zmp-1::GFP, a molecular marker that distinguishes these two fates, is expressed in vulE cells, but not vulF cells. We demonstrate that a short-range AC signal is required to ensure that the pattern of vulE and vulF fates is properly established. In addition, signaling between the inner and outer 1 degrees VPC descendants, as well as intrinsic polarity of the 1 degrees VPC daughters, is involved in the asymmetric divisions of the 1 degrees VPC daughters and the proper orientation of the outcome. Finally, we provide evidence that RAS signaling is used during this new AC signaling event, while the Wnt receptor LIN-17 appears to mediate signaling between the inner and outer 1 degrees VPC descendants.

The evolution of cell lineage in nematodes

Development ◽  
1994 ◽  
Vol 1994 (Supplement) ◽  
pp. 85-95
Author(s):  
Ralf J. Sommer ◽  
Lynn K. Carta ◽  
Paul W. Sternberg
Keyword(s):  
Cell Lineage ◽  
Experimental System ◽  
Nematode Species ◽  
Cell Fates ◽  
Equivalence Group ◽  
Vulval Development ◽  
C Elegans ◽  
Somatic Gonad ◽  
Vulval Precursor Cell ◽  
P Cells

The invariant development of free-living nematodes combined with the extensive knowledge of Caenorhabditis elegans developmental biology provides an experimental system for an analysis of the evolution of developmental mechanisms. We have collected a number of new nematode species from soil samples. Most are easily cultured and their development can be analyzed at the level of individual cells using techniques standard to Caenorhabditis. So far, we have focused on differences in the development of the vulva among species of the families Rhabditidae and Panagrolaimidae. Preceding vulval development, twelve Pn cells migrate into the ventral cord and divide to produce posterior daughters [Pn.p cells] whose fates vary in a position specific manner [from P1.p anterior to P12.p posterior]. In C. elegans hermaphrodites, P(3-8).p are tripotent and form an equivalence group. These cells can express either of two vulval fates (1° or 2°) in response to a signal from the anchor cell of the somatic gonad, or a non-vulval fate (3°), resulting in a 3°-3°-2°-1°-2°-3° pattern of cell fates. Evolutionary differences in vulval development include the number of cells in the vulval equivalence group, the number of 1° cells, the number of progeny generated by each vulval precursor cell, and the position of VPCs before morphogenesis. Examples of three Rhabditidae genera have a posterior vulva in the position of P9-P11 ectoblasts. In Cruznema tripartitum, P(5-7).p form the vulva as in Caenorhabditis, but they migrate posteriorly before dividing. Induction occurs after the gonad grows posteriorly to the position of P(5-7).p cells. In two other species, Mesorhabditis sp. PS 1179 and Teratorhabditis palmarum, we have found changes in induction and competence with respect to their presumably more C. elegans-like ancestor. In Mesorhabditis, P(5-7).p form the vulva after migrating to a posterior position. However, the gonad is not required to specify the pattern of cell fates 3°-2°-1°-2°-3°. Moreover, the Pn.p cells are not equivalent in their potentials to form the vulva. A regulatory constraint in this family thus forces the same set of precursors to generate the vulva, rather than more appropriately positioned Pn.p cells.

Two homologous regulatory genes, lin-12 and glp-1, have overlapping functions

Development ◽  
1991 ◽  
Vol 112 (1) ◽  
pp. 231-240 ◽  
Author(s):  
E.J. Lambie ◽  
J. Kimble
Keyword(s):  
Gene Expression ◽  
Double Mutant ◽  
Transmembrane Proteins ◽  
Cell Interactions ◽  
Loss Of Function ◽  
Cell Fates ◽  
Single Mutant ◽  
C Elegans ◽  
Homologous Genes ◽  
Mutant Phenotypes

Two homologous genes, lin-12 and glp-1, encode transmembrane proteins required for regulatory cell interactions during C. elegans development. Based on their single mutant phenotypes, each gene has been thought to govern a distinct set of cell fates. We show here that lin-12 and glp-1 are functionally redundant during embryogenesis: Unlike either single mutant, the lin-12 glp-1 double mutant dies soon after hatching. Numerous cellular defects can be observed in these Lag (for lin-12 and glp-1) double mutants. Furthermore, we have identified two genes, lag-1 and lag-2, that appear to be required for both lin-12 and glp-1-mediated cell interactions. Strong loss-of-function lag mutants are phenotypically indistinguishable from the lin-12 glp-1 double; weak lag mutants have phenotypes typical of lin-12 and glp-1 single mutants. We speculate that the lin-12 and glp-1 proteins are biochemically interchangeable and that their divergent roles in development may rely largely on differences in gene expression.

scholarly journals Kidney‐in‐a‐lymph node: A novel organogenesis assay to model human renal development and test nephron progenitor cell fates

2019 ◽  
Vol 13 (9) ◽  
pp. 1724-1731 ◽  
Author(s):  
Maria Giovanna Francipane ◽  
Bing Han ◽  
Leif Oxburgh ◽  
Sunder Sims‐Lucas ◽  
Zhongwei Li ◽  
...  
Keyword(s):  
Lymph Node ◽  
Progenitor Cell ◽  
Renal Development ◽  
Cell Fates ◽  
Nephron Progenitor
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