scholarly journals Environmental pheromone and endocrine signals correct heterochronic developmental phenotypes caused by insufficient expression of let-7 family microRNAs in C. elegans

2019 ◽  
Author(s):  
Orkan Ilbay ◽  
Victor Ambros
Keyword(s):  
Signaling Pathways ◽  
Cell Fate ◽  
Developmental Trajectories ◽  
Cell Lineage ◽  
Nuclear Hormone Receptor ◽  
Developmental Trajectory ◽  
Cell Fates ◽  
C Elegans ◽  
Developmental Progression ◽  
Endocrine Signaling

SummaryAdverse environmental conditions can affect rates of animal developmental progression and lead to temporary developmental quiescence (diapause), exemplified by the dauer larva stage of the nematode Caenorhabditis elegans. Remarkably, patterns of cell division and temporal cell fate progression in C. elegans larvae are not affected by changes in developmental trajectory. However, the underlying physiological and gene regulatory mechanisms that ensure robust developmental patterning despite substantial plasticity in developmental progression are largely unknown. Here, we report that diapause-inducing environmental pheromone and endocrine signals correct heterochronic developmental cell lineage defects caused by insufficient expression of let-7 family microRNAs in C. elegans. Two conserved endocrine signaling pathways, DAF-7/TGF-β and DAF-2/Insulin, that confer on the larva diapause/non-diapause alternative developmental trajectories, interact with the nuclear hormone receptor, DAF-12, to initiate and regulate a rewiring of the genetic circuitry controlling temporal cell fates. This rewiring includes: 1) repression of the DAF-12 ligand-activated expression of let-7 family microRNAs, and 2) engagement of a novel ligand-independent DAF-12 activity to downregulate the critical let-7 family target Hunchback-like-1 (HBL-1). This alternative HBL-1 downregulation program is responsible for correcting let-7 family insufficiency phenotypes and it requires the activities of certain heterochronic genes, lin-46, lin-4 and nhl-2, that are previously associated with an altered genetic program in post-diapause animals. Our results show how environmental pheromones and endocrine signaling pathways can coordinately regulate both developmental progression and cell fate transitions in C. elegans larvae under stress, so that the developmental schedule of cell fates remains unaffected by changes in developmental trajectory.

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.

scholarly journals Morphogenesis of the C. elegans hermaphrodite uterus

Development ◽  
1996 ◽  
Vol 122 (11) ◽  
pp. 3617-3626 ◽  
Author(s):  
A.P. Newman ◽  
J.G. White ◽  
P.W. Sternberg
Keyword(s):  
Cell Fate ◽  
Cell Lineage ◽  
Cell Types ◽  
Cell Interaction ◽  
Cell Fate Decision ◽  
Cell Fates ◽  
C Elegans ◽  
A Cell ◽  
Anchor Cell ◽  
Fate Decision

We have undertaken electron micrographic reconstruction of the Caenorhabditis elegans hermaphrodite uterus and determined the correspondence between cells defined by their lineage history and differentiated cell types. In this organ, many cells do not move during morphogenesis and the cell lineage may function to put cells where they are needed. Differentiated uterine cell types include the toroidal ut cells that make structural epithelium, and specialized utse and uv cells that make the connection between the uterus and the vulva. A cell fate decision in which the anchor cell (AC) induces adjacent ventral uterine intermediate precursor cells to adopt the pi fate, rather than the ground state rho, has profound consequences for terminal differentiation: all pi progeny are directly involved in making the uterine-vulval connection whereas all rho progeny contribute to ut toroids or the uterine-spermathecal valve. In addition to specifying certain uterine cell fates, the AC also induces the vulva. Its multiple inductions thereby function to coordinate the connection of an internal to an external epithelium. The AC induces the pi cells and ultimately fuses with a subset of their progeny. This is an example of reciprocal cell-cell interaction that can be studied at single cell resolution. The AC is thus a transitory cell type that plays a pivotal role in organizing the morphogenesis of the uterine-vulval connection.

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.

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.

scholarly journals A Gene Network Model for Developing Cell Lineages

2005 ◽  
Vol 11 (3) ◽  
pp. 249-267 ◽  
Author(s):  
Nicholas Geard ◽  
Janet Wiles
Keyword(s):  
Gene Network ◽  
Temporal Dynamics ◽  
Developmental Trajectories ◽  
Cell Lineage ◽  
Cell Types ◽  
External Input ◽  
Sufficient Information ◽  
Cell Lineages ◽  
C Elegans ◽  
Task Definition

Biological development is a remarkably complex process. A single cell, in an appropriate environment, contains sufficient information to generate a variety of differentiated cell types, whose spatial and temporal dynamics interact to form detailed morphological patterns. While several different physical and chemical processes play an important role in the development of an organism, the locus of control is the cell's gene regulatory network. We designed a dynamic recurrent gene network (DRGN) model and evaluated its ability to control the developmental trajectories of cells during embryogenesis. Three tasks were developed to evaluate the model, inspired by cell lineage specification in C. elegans, describing the variation in gene activity required for early cell diversification, combinatorial control of cell lineages, and cell lineage termination. Three corresponding sets of simulations compared performance on the tasks for different gene network sizes, demonstrating the ability of DRGNs to perform the tasks with minimal external input. The model and task definition represent a new means of linking the fundamental properties of genetic networks with the topology of the cell lineages whose development they control.

scholarly journals A cohort of Caenorhabditis species lacking the highly conserved let-7 microRNA

2020 ◽  
Author(s):  
Charles Nelson ◽  
Victor Ambros
Keyword(s):  
Cell Fate ◽  
Nematode Species ◽  
Loss Of Function ◽  
Animal Development ◽  
C Elegans ◽  
Adult Transition ◽  
Developmental Progression ◽  
Caenorhabditis Species ◽  
Heterochronic Gene ◽  
Bilaterian Animal

ABSTRACTlet-7 is a highly conserved microRNA with critical functions integral to cell fate specification and developmental progression in diverse animals. In Caenorhabditis elegans, let-7 is a component of the heterochronic (developmental timing) gene regulatory network, and loss-of-function mutations of let-7 result in lethality during the larval to adult transition due to misregulation of the conserved let-7 target, lin-41. To date, no bilaterian animal lacking let-7 has been characterized. In this study, we identify a cohort of nematode species within the genus Caenorhabditis, closely related to C. elegans, that lack the let-7 microRNA, owing to absence of the let-7 gene. Using C. sulstoni as a representative let-7-lacking species to characterize normal larval development in the absence of let-7, we demonstrate that, except for the lack of let-7, the heterochronic gene network is otherwise functionally conserved. We also report that species lacking let-7 contain a group of divergent let-7 orthologs -- also known as the let-7-family of microRNAs -- that have apparently assumed the role of targeting the lin-41 mRNA.Summary StatementWe have identified a group of Caenorhabditis species that lack let-7a, an otherwise highly conserved and nearly ubiquitous microRNA that was previously thought to be critical to bilaterian animal development.

scholarly journals Physically asymmetric division of the C. elegans zygote ensures invariably successful embryogenesis

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Radek Jankele ◽  
Rob Jelier ◽  
Pierre Gönczy
Keyword(s):  
Cell Fate ◽  
Cell Cycle Progression ◽  
Cell Lineage ◽  
External Compression ◽  
Cycle Progression ◽  
Spindle Positioning ◽  
C Elegans ◽  
Daughter Cells ◽  
Asymmetric Divisions ◽  
Cell Positioning

Asymmetric divisions that yield daughter cells of different sizes are frequent during early embryogenesis, but the importance of such a physical difference for successful development remains poorly understood. Here, we investigated this question using the first division ofCaenorhabditis elegansembryos, which yields a large AB cell and a small P1cell. We equalized AB and P1sizes using acute genetic inactivation or optogenetic manipulation of the spindle positioning protein LIN-5. We uncovered that only some embryos tolerated equalization, and that there was a size asymmetry threshold for viability. Cell lineage analysis of equalized embryos revealed an array of defects, including faster cell cycle progression in P1descendants, as well as defects in cell positioning, division orientation, and cell fate. Moreover, equalized embryos were more susceptible to external compression. Overall, we conclude that unequal first cleavage is essential for invariably successful embryonic development ofC. elegans.

scholarly journals A cohort of Caenorhabditis species lacking the highly conserved let-7 microRNA

2021 ◽  
Author(s):  
Charles Nelson ◽  
Victor Ambros
Keyword(s):  
Cell Fate ◽  
Nematode Species ◽  
Loss Of Function ◽  
C Elegans ◽  
Adult Transition ◽  
Developmental Progression ◽  
Caenorhabditis Species ◽  
Heterochronic Gene ◽  
Bilaterian Animal

Abstract The let-7 gene encodes a highly conserved microRNA with critical functions integral to cell fate specification and developmental progression in diverse animals. In Caenorhabditis elegans, let-7 is a component of the heterochronic (developmental timing) gene regulatory network, and loss-of-function mutations of let-7 result in lethality during the larval to adult transition due to misregulation of the conserved let-7 target, lin-41. To date, no bilaterian animal lacking let-7 has been characterized. In this study, we identify a cohort of nematode species within the genus Caenorhabditis, closely related to C. elegans, that lack the let-7 microRNA, owing to absence of the let-7 gene. Using C. sulstoni as a representative let-7-lacking species to characterize normal larval development in the absence of let-7, we demonstrate that, except for the lack of let-7, the heterochronic gene network is otherwise functionally conserved. We also report that species lacking let-7 contain a group of divergent let-7 paralogs—also known as the let-7-family of microRNAs—that have apparently assumed the role of targeting the lin-41 mRNA.

scholarly journals Gene expression profiling of epidermal cell types in C. elegans using Targeted-DamID

Development ◽  
2021 ◽  
Author(s):  
Dimitris Katsanos ◽  
Mar Ferrando-Marco ◽  
Iqrah Razzaq ◽  
Gabriel Aughey ◽  
Tony Southall ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Epidermal Cell ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cell Types ◽  
Specific Gene ◽  
C Elegans ◽  
Seam Cell ◽  
Developmental Progression

The epidermis of Caenorhabditis elegans is an essential tissue for survival as it contributes to the formation of the cuticle barrier, as well as facilitates developmental progression and animal growth. Most of the epidermis consists of the hyp7 hypodermal syncytium, the nuclei of which are largely generated by the seam cells that exhibit stem cell-like behaviour during development. How the seam cell progenitors differ transcriptionally from the differentiated hypodermis is poorly understood. Here, we introduce Targeted DamID (TaDa) in C. elegans as a method for identifying genes expressed within a tissue of interest without cell isolation. We show that TaDa signal enrichment profiles can be used to identify genes transcribed in the epidermis and use this method to resolve differences in gene expression between the seam cells and the hypodermis. We finally predict and functionally validate new transcription and chromatin factors acting in seam cell development. These findings provide insights into cell-type-specific gene expression profiles likely associated with epidermal cell fate patterning.

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