A hierarchy of regulatory genes controls a larva-to-adult developmental switch in C. elegans

doi:10.1016/0092-8674(89)90171-2

Cell

Volume 57, Issue 1, 7 April 1989, Pages 49-57

https://doi.org/10.1016/0092-8674(89)90171-2 Get rights and content

Abstract

The heterochronic genes lin-4, lin-14, lin-29 control the timing of specific postembryonic developmental events in C. elegans. The experiments described here examine how these four genes interact to control a particular stage-specific event of the lateral hypodermal cell lineages. This event, termed the “larva-to-adult switch” (L/A switch), involves several coordinate changes in the behavior of hypodermal cells at the fourth molt: cessation of cell division, formation of adult (instead of larval) cuticle, cell fusion, and cessation of the molting cycle. The phenotypes of multiply mutant strains suggest a model wherein the L/A switch is controlled by the stage-specific activity of a regulatory hierarchy: At early stages of wild-type development, lin-14 and lin-28 inhibit lin-29 and thus prevent switching. Later, lin-4 inhibits lin-14 and lin-28, allowing activation of lin-29, which in turn triggers the switch in the L4 stage. lin-29 may activate the L/A switch by regulating genes that control cell division, differentiation, and stage-specific gene expression in hypodermal cells.

References (30)

V.R. Ambros et al.
Heterochronic mutants of the nematode Caenorhabditis elegans
Science
(1984)
V.R. Ambros et al.
The lin-14 locus of Caenorhabditis elegans controls the time of expression of specific postembryonic developmental events
Genes Dev.
(1987)
K.V. Anderson et al.
Establishment of dorsal-ventral polarity in the Drosophila embryo: genetic studies on the role of the Toll gene product
Cell
(1985)
B.S. Baker et al.
Sex and the single cell: on the action of major loci affecting sex determination in Drosophila melanogaster
Genetics
(1980)
S. Brenner
The genetics of C. elegans
Genetics
(1974)
M. Chalfie et al.
Mutations that lead to reiterations in the cell lineages of C. elegans
Cell
(1981)
G.N. Cox et al.
Stage-specific patterns of collagen gene-expression during development of C. elegans
Mol. Cell. Biol.
(1985)
G.N. Cox et al.
The cuticle of C. elegans. II. Stage-specific changes in ultrastructure and protein composition during postembryonic development
Dev. Biol.
(1981)
L. DeLong et al.
Assessment of X chromosome dosage compensation in Caenorhabditis elegans by phenotypic analysis of lin-14
Genetics
(1987)
M.K. Edwards et al.
Location of specific messenger RNAs in C. elegans by cytological hybridization
Dev. Biol.
(1983)

E.L. Ferguson et al.

A genetic pathway for the specification of the vulval cell lineages of C. elegans

Nature

(1987)

A. Fodor et al.

Isolation and phenocritical period-analysis of conditional and non-conditional developmental mutants in C. elegans

Acta Biol. Acad. Sci. Hung.

(1982)

R.K. Herman

Crossover suppressors and balanced recessive lethals in C. elegans

Genetics

(1978)

J. Hodgkin

More sex-determination mutants of C. elegans

Genetics

(1980)

J. Hodgkin

Males, hermaphrodites and females: sex determination in C. elegans

Trends Genet.

(1985)

Cited by (297)

Molecular mechanism governing RNA-binding property of mammalian TRIM71 protein
2024, Science Bulletin
TRIM71 is an RNA-binding protein with ubiquitin ligase activity. Numerous functions of mammalian TRIM71, including cell cycle regulation, embryonic stem cell (ESC) self-renewal, and reprogramming of pluripotent stem cells, are related to its RNA-binding property. We previously reported that a long noncoding RNA (lncRNA) Trincr1 interacts with mouse TRIM71 (mTRIM71) to repress FGF/ERK pathway in mouse ESCs (mESCs). Herein, we identify an RNA motif specifically recognized by mTRIM71 from Trincr1 RNA, and solve the crystal structure of the NHL domain of mTRIM71 complexed with the RNA motif. Similar to the zebrafish TRIM71, mTRIM71 binds to a stem-loop structured RNA fragment of Trincr1, and an adenosine base at the loop region is crucial for the mTRIM71 interaction. We map similar hairpin RNAs preferably bound by TRIM71 in the mRNA UTRs of the cell-cycle related genes regulated by TRIM71. Furthermore, we identify key residues of mTRIM71, conserved among mammalian TRIM71 proteins, required for the RNA-binding property. Single-site mutations of these residues significantly impair the binding of TRIM71 to hairpin RNAs in vitro and to mRNAs of Cdkn1a/p21 and Rbl2/p130 in mESCs. Furthermore, congenital hydrocephalus (CH) specific mutation of mTRIM71 impair its binding to the RNA targets as well. These results reveal molecular mechanism behind the recognition of RNA by mammalian TRIM71 and provide insights into TRIM71 related diseases.
A circadian-like gene network programs the timing and dosage of heterochronic miRNA transcription during C. elegans development
2023, Developmental Cell
Development relies on the exquisite control of both the timing and the levels of gene expression to achieve robust developmental transitions. How cis- and trans-acting factors control both aspects simultaneously is unclear. We show that transcriptional pulses of the temporal patterning microRNA (miRNA) lin-4 are generated by two nuclear hormone receptors (NHRs) in C. elegans, NHR-85 and NHR-23, whose mammalian orthologs, Rev-Erb and ROR, function in the circadian clock. Although Rev-Erb and ROR antagonize each other to control once-daily transcription in mammals, NHR-85/NHR-23 heterodimers bind cooperatively to lin-4 regulatory elements to induce a single pulse of expression during each larval stage. Each pulse’s timing, amplitude, and duration are dictated by the phased expression of these NHRs and the C. elegans Period ortholog, LIN-42, that binds to and represses NHR-85. Therefore, during nematode temporal patterning, an evolutionary rewiring of circadian clock components couples the timing of gene expression to the control of transcriptional dosage.
Fecundity, in vitro early larval development and karyotype of the zoonotic nematode Anisakis pegreffii
2023, Veterinary Parasitology
The in vitro life cycle of zoonotic helminths is an essential tool for -omic translational studies focused on disease control and treatment. Anisakiosis is an emerging zoonosis contracted by the ingestion of raw or undercooked fish infected with the third stage larvae (L3) of two sibling species Anisakis simplex sensu stricto (s.s.) and Anisakis pegreffii, the latter being the predominant species in the Mediterranean basin. Recently, in vitro culture of A. pegreffii has been developed to enable fast and large-scale production of fertile adults. However, the conditions for larval development from hatching to infective L3 were not fulfilled to complete the cycle. Herein, we used a Drosophila medium supplemented with chicken serum and adjusted different osmolarities to maintain the culture of L3 hatched from eggs for up to 17 weeks. The highest survival rate was observed in the medium with the highest osmolarities, which also allowed the highest larval exsheathment rate. Key morphological features of embryogenesis and postembryogenesis studied by transmission electron microscopy revealed that the excretory gland cell is differentiated already up to 48 h post-hatching. Extracellular vesicles and cell-free mitochondria are discharged between the two cuticle sheets of the second stage larvae (L2). Contemporarly cultivated, two populations of adult A. simplex s.s. and A. pegreffii reached an average production of 29,914.05 (± 27,629.36) and 24,370.96 (± 12,564.86) eggs/day/female, respectively. The chromosome spreads of A. pegreffii obtained from mature gonads suggests a diploid karyotype formula of 2n = 18. The development of a reliable protocol for the in vitro culture of a polyxenous nematode such as Anisakis spp. will serve to screen for much needed novel drug targets, but also to study the intricated and unknown ecological and physiological traits of these trophically transmitted marine nematodes.
Body stiffness is a mechanical property that facilitates contact-mediated mate recognition in Caenorhabditis elegans
2023, Current Biology
Physical contact is prevalent in the animal kingdom to recognize suitable mates by decoding information about sex, species, and maturity. Although chemical cues for mate recognition have been extensively studied, the role of mechanical cues remains elusive. Here, we show that C. elegans males recognize conspecific and reproductive mates through short-range cues, and that the attractiveness of potential mates depends on the sex and developmental stages of the hypodermis. We find that a particular group of cuticular collagens is required for mate attractiveness. These collagens maintain body stiffness to sustain mate attractiveness but do not affect the surface properties that evoke the initial step of mate recognition, suggesting that males utilize multiple sensory mechanisms to recognize suitable mates. Manipulations of body stiffness via physical interventions, chemical treatments, and 3D-printed bionic worms indicate that body stiffness is a mechanical property for mate recognition and increases mating efficiency. Our study thus extends the repertoire of sensory cues of mate recognition in C. elegans and provides a paradigm to study the important roles of mechanosensory cues in social behaviors.
Temporal transitions in the postembryonic nervous system of the nematode Caenorhabditis elegans: Recent insights and open questions
2023, Seminars in Cell and Developmental Biology
Citation Excerpt :
However, genetic programs that specify temporal transitions in post-mitotic neurons during postembryonic development have been much less considered. Post-mitotic, temporal regulatory programs in the nervous system of C. elegans have been identified by considering the function of regulatory programs that were initially identified by their role in controlling the lineage patterns of dividing blast cells [6,8,20]. These lineage patterns are highly stereotyped, both in occurrence and in developmental timing throughout specific larval stages.
After the generation, differentiation and integration into functional circuitry, post-mitotic neurons continue to change certain phenotypic properties throughout postnatal juvenile stages until an animal has reached a fully mature state in adulthood. We will discuss such changes in the context of the nervous system of the nematode C. elegans, focusing on recent descriptions of anatomical and molecular changes that accompany postembryonic maturation of neurons. We summarize the characterization of genetic timer mechanisms that control these temporal transitions or maturational changes, and discuss that many but not all of these transitions relate to sexual maturation of the animal. We describe how temporal, spatial and sex-determination pathways are intertwined to sculpt the emergence of cell-type specific maturation events. Finally, we lay out several unresolved questions that should be addressed to move the field forward, both in C. elegans and in vertebrates.
Small RNA networking: host-microbe interaction in food crops
2023, Plant Small RNA in Food Crops
To keep pace with the increasing demand of world population we have to increase the agriculture production and advancement in technology to improve food security. The concern intensifies after an outbreak of COVID – 19 pandemic which further deteriorate nutritional and food security status in vulnerable groups. According to a UNICEF report, 690 million people are still suffering from hunger mostly from developing countries (https://www.unicef.org/reports/state-of-food-security-and-nutrition-2020). This figure is expected to reach 840 million by 2030 (https://www.wfp.org/publications/hunger-map-2020) is quite alarming. Further study and information on small RNA and their respective target genes and the RNAi machinery will open up novel avenues for crop protection. Small RNAs are major players in regulating plant response during plant-microbe interaction. They are short non-coding regulatory molecules that regulate plant cellular processes, like development, stress response, metabolism, and genome integrity through inducing RNAinterference (RNAi). There are various types of small RNA (miRNA, siRNA, piRNA, etc) networks that up-down regulate target gene expression and effects plant immunity. The interaction between plants and microbes could be beneficial or pathogenic in nature. An insight into the molecular relation of small RNAs with microbes and plants will improve design of innovative strategies for crop improvement and enhance the production of food, wood and fiber.

View all citing articles on Scopus

View full text

Cell

ArticleA hierarchy of regulatory genes controls a larva-to-adult developmental switch in C. elegans

Abstract

Heterochronic mutants of the nematode Caenorhabditis elegans

Science

The lin-14 locus of Caenorhabditis elegans controls the time of expression of specific postembryonic developmental events

Genes Dev.

Establishment of dorsal-ventral polarity in the Drosophila embryo: genetic studies on the role of the Toll gene product

Cell

Sex and the single cell: on the action of major loci affecting sex determination in Drosophila melanogaster

Genetics

The genetics of C. elegans

Genetics

Mutations that lead to reiterations in the cell lineages of C. elegans

Cell

Stage-specific patterns of collagen gene-expression during development of C. elegans

Mol. Cell. Biol.

The cuticle of C. elegans. II. Stage-specific changes in ultrastructure and protein composition during postembryonic development

Dev. Biol.

Assessment of X chromosome dosage compensation in Caenorhabditis elegans by phenotypic analysis of lin-14

Genetics

Location of specific messenger RNAs in C. elegans by cytological hybridization

Dev. Biol.

A genetic pathway for the specification of the vulval cell lineages of C. elegans

Nature

Isolation and phenocritical period-analysis of conditional and non-conditional developmental mutants in C. elegans

Acta Biol. Acad. Sci. Hung.

Crossover suppressors and balanced recessive lethals in C. elegans

Genetics

More sex-determination mutants of C. elegans

Genetics

Males, hermaphrodites and females: sex determination in C. elegans

Trends Genet.

Article
A hierarchy of regulatory genes controls a larva-to-adult developmental switch in C. elegans