Escargot (transcription factor)

Last updated
Escargot
Identifiers
Organism Drosophila melanogaster
SymbolDmel/esg
UniProt P25932
Search for
Structures Swiss-model
Domains InterPro

Escargot (esg) is a transcription factor expressed in Drosophila melanogaster . It is responsible for the maintenance of intestinal stem cells and is used as a marker for those types of cells in Drosophila . [1] [2] [3] Apart from its expression in the gut, esg is also expressed in expressed in germline stem cells and cyst stem cells of the testis [4] [5] and, during development, in neural stem cells and imaginal disks. [6] [7] [8]

Contents

Discovery

In the year 1992, Mary Whiteley and coworkers identified a gene which is very similar to Drosophila Snail gene and named it escargot. They found that it encodes for zinc finger like snail related genes. [1]

Pathways associated with escargot

Delta-Notch signaling

Esg acts through the Notch signaling pathway to repress differentiation-related genes in the Drosophila gut. Intestinal stem cells produce the ligand for the Notch receptor i.e.,Delta which activates a transcriptional program that leads to the differentiation of enteroblasts to enterocytes and Escargot represses this. [2] Esg and Scratch act redundantly to determine neural commitment in sensory cells by antagonizing Notch activity which is required for neuronal fate determination by regulating the number of neural precursor cells and also by directing the cells fates to their neural type lineages. Esg along with scratch were reported to be involved in assigning neural commitment and induce neural cell type fates in Drosophila mechanosensory organ lineage cells. [9]

Insulin receptor pathway

Esg is required for the maintenance of somatic cyst stem cells in their stem state. The testis in Drosophila has two types of stem cells: the germline stem cells and the somatic cyst stem cells. Germline stem cells divide to generate a daughter gonialblast and a germline stem cell. The gonialblast undergoes mitotic transit-amplifying divisions to produce spermatocytes which will eventually give rise to haploid spermatids. On the other hand, cyst stem cells generate cyst cells and cyst stem cells. Cyst stem cells/cyst cells encapsulate the gonialblast and differentiate with differentiating germline and act analogously to the mammalian sertoli cells. Drosophila insulin-like peptide signaling pathway is required for the differentiation of dividing cyst stem cells. Esg overexpression enhances the activity of imaginal morphogenesis protein-late 2 (ImpL2) (fly homolog of mammalian insulin-like growth factor binding protein IGFBP7), which is required to prevent the differentiation of dividing cyst stem cells and there by maintains the cyst stem cells in stem cell state. [10]

FGF signaling

Fibroblast growth factor signaling is important for trachea development in insects. Branching morphogenesis of the tracheal system in Drosophila is governed by FGF signaling. The primordial tip cells expressing Branchless/Breathless will initiate the primary branching and migration. The tip cells get differentiated into fusion cells or terminal cells. Fusion cells will get differentiated into different type of cells while terminal cells form cytoplasmic extensions with intracellular lumen. Esg regulates the diversification of branching tip cells by inhibiting the FGF signaling. [11]

Esg homologs

Phylogenetic tree of D. melanogaster esg sequence Esg phylogenic tree.png
Phylogenetic tree of D. melanogaster esg sequence

The Snail-related zinc-finger transcription factor family has been implicated in stem cell maintenance in the model insect, the fly D. melanogaster. [2] There are three Snail family members in D. melanogaster: escargot (esg), snail, and worniu. After the initial cloning of snail in D. melanogaster, additional snail-orthlogues have been isolated in other animals including Tribolium castaneum (beetle), Achaearanea tepidariorum (spider), the frog Xenopus laevis, chicken, and mouse. [12] Besides snail, D. melanogaster encodes five snail paralogs including esg, worniu, scratch, scratch-like 1, and scratch-like 2. [12] The Snail family is part of the larger Snail superfamily, which comprises Snail and Scratch families. [13] The Snail family members snail, esg and worniu are involved in forming variable structures in D. melanogaster by functioning in several cellular process like cell behavior, cell shape, cell asymmetric divisions, cell fate regulation and cell differentiation, [12] while D. melanogaster scratch mainly promotes neural cell fate. [14] Recently, esg orthologue was identified in the genome of the leipdopteran Chloridea virescens . [15]

Esg and tumors

Intra-tumour heterogeneity (ITH) is the altered and diverse morphological, genetic, epigenetic, transcriptomic and metabolomic states of cancerous cells. The somatic epithelial cells of the Drosophila ovary emerge from germline stem cells to form polarized follicle cells that establish the monolayered epithelia which surrounds the germline cells within an egg chamber. Drosophila ovarian follicle cell model was used to study the ITH. Heterogeneity was induced in the follicle cells in-situ. It was discovered that loss of cell polarity induces heterogenous multilayering. Esg was upregulated in the heterogenous cell population down stream of Upd/Jak-STAT signaling and maintains the non-polar cells. This can be extrapolated to the cancer-associated fibroblasts which communicate with tumour cells via IL-6/STAT3 and this regulates cancer stem cell maintenance via Snail. [16]

Functions

Hypothesized function of escargot in insect gut ISC - Instestinal stem cell; EE - Enteroendocrine cell Esg stemness.png
Hypothesized function of escargot in insect gut ISC - Instestinal stem cell; EE - Enteroendocrine cell

Esg is expressed in the blastoderm stage in dorsal surface of the embryo, cephalic furrow, and lateral and medial columns of neurectoderm. During the latter stage of embryogenesis, esg is expressed in primordial cells responsible for the development of wings, halteres, genital and abdominal tissues. [1] [17] [6] [18] Other functions of the esg include:

Related Research Articles

In cellular biology, a somatic cell, or vegetal cell, is any biological cell forming the body of a multicellular organism other than a gamete, germ cell, gametocyte or undifferentiated stem cell. Somatic cells compose the body of an organism and divide through mitosis.

<span class="mw-page-title-main">Germ cell</span> Gamete-producing cell

A germ cell is any cell that gives rise to the gametes of an organism that reproduces sexually. In many animals, the germ cells originate in the primitive streak and migrate via the gut of an embryo to the developing gonads. There, they undergo meiosis, followed by cellular differentiation into mature gametes, either eggs or sperm. Unlike animals, plants do not have germ cells designated in early development. Instead, germ cells can arise from somatic cells in the adult, such as the floral meristem of flowering plants.

<span class="mw-page-title-main">Mosaic (genetics)</span> Condition in multi-cellular organisms

Mosaicism or genetic mosaicism is a condition in which a multicellular organism possesses more than one genetic line as the result of genetic mutation. This means that various genetic lines resulted from a single fertilized egg. Mosaicism is one of several possible causes of chimerism, wherein a single organism is composed of cells with more than one distinct genotype.

In vertebrates, a neuroblast or primitive nerve cell is a postmitotic cell that does not divide further, and which will develop into a neuron after a migration phase. In invertebrates such as Drosophila, neuroblasts are neural progenitor cells which divide asymmetrically to produce a neuroblast, and a daughter cell of varying potency depending on the type of neuroblast. Vertebrate neuroblasts differentiate from radial glial cells and are committed to becoming neurons. Neural stem cells, which only divide symmetrically to produce more neural stem cells, transition gradually into radial glial cells. Radial glial cells, also called radial glial progenitor cells, divide asymmetrically to produce a neuroblast and another radial glial cell that will re-enter the cell cycle.

<span class="mw-page-title-main">Germline mutation</span> Inherited genetic variation

A germline mutation, or germinal mutation, is any detectable variation within germ cells. Mutations in these cells are the only mutations that can be passed on to offspring, when either a mutated sperm or oocyte come together to form a zygote. After this fertilization event occurs, germ cells divide rapidly to produce all of the cells in the body, causing this mutation to be present in every somatic and germline cell in the offspring; this is also known as a constitutional mutation. Germline mutation is distinct from somatic mutation.

Polycomb-group proteins are a family of protein complexes first discovered in fruit flies that can remodel chromatin such that epigenetic silencing of genes takes place. Polycomb-group proteins are well known for silencing Hox genes through modulation of chromatin structure during embryonic development in fruit flies. They derive their name from the fact that the first sign of a decrease in PcG function is often a homeotic transformation of posterior legs towards anterior legs, which have a characteristic comb-like set of bristles.

In developmental biology, the cells that give rise to the gametes are often set aside during embryonic cleavage. During development, these cells will differentiate into primordial germ cells, migrate to the location of the gonad, and form the germline of the animal.

<span class="mw-page-title-main">Piwi</span> Genes and regulatory proteins

Piwi genes were identified as regulatory proteins responsible for stem cell and germ cell differentiation. Piwi is an abbreviation of P-elementInduced WImpy testis in Drosophila. Piwi proteins are highly conserved RNA-binding proteins and are present in both plants and animals. Piwi proteins belong to the Argonaute/Piwi family and have been classified as nuclear proteins. Studies on Drosophila have also indicated that Piwi proteins have no slicer activity conferred by the presence of the Piwi domain. In addition, Piwi associates with heterochromatin protein 1, an epigenetic modifier, and piRNA-complementary sequences. These are indications of the role Piwi plays in epigenetic regulation. Piwi proteins are also thought to control the biogenesis of piRNA as many Piwi-like proteins contain slicer activity which would allow Piwi proteins to process precursor piRNA into mature piRNA.

Stem-cell niche refers to a microenvironment, within the specific anatomic location where stem cells are found, which interacts with stem cells to regulate cell fate. The word 'niche' can be in reference to the in vivo or in vitro stem-cell microenvironment. During embryonic development, various niche factors act on embryonic stem cells to alter gene expression, and induce their proliferation or differentiation for the development of the fetus. Within the human body, stem-cell niches maintain adult stem cells in a quiescent state, but after tissue injury, the surrounding micro-environment actively signals to stem cells to promote either self-renewal or differentiation to form new tissues. Several factors are important to regulate stem-cell characteristics within the niche: cell–cell interactions between stem cells, as well as interactions between stem cells and neighbouring differentiated cells, interactions between stem cells and adhesion molecules, extracellular matrix components, the oxygen tension, growth factors, cytokines, and the physicochemical nature of the environment including the pH, ionic strength and metabolites, like ATP, are also important. The stem cells and niche may induce each other during development and reciprocally signal to maintain each other during adulthood.

<span class="mw-page-title-main">Ovariole</span>

An ovariole is a tubular component of the insect ovary, and the basic unit of egg production. Each ovariole is composed of a germarium at the anterior tip, a set of developing oocytes contained within follicles, and a posterior connection to a common oviduct. While most insects have two ovaries, the number of ovarioles within each ovary varies across insect species. This number may also be variable across individuals within a species, or between the left and right ovaries within an individual.

Vasa is an RNA binding protein with an ATP-dependent RNA helicase that is a member of the DEAD box family of proteins. The vasa gene is essential for germ cell development and was first identified in Drosophila melanogaster, but has since been found to be conserved in a variety of vertebrates and invertebrates including humans. The Vasa protein is found primarily in germ cells in embryos and adults, where it is involved in germ cell determination and function, as well as in multipotent stem cells, where its exact function is unknown.

<span class="mw-page-title-main">DM domain</span> Protein family

In molecular biology the DM domain is a protein domain first discovered in the doublesex proteins of Drosophila melanogaster and is also seen in C. elegans and mammalian proteins. In D. melanogaster the doublesex gene controls somatic sexual differentiation by producing alternatively spliced mRNAs encoding related sex-specific polypeptides. These proteins are believed to function as transcription factors on downstream sex-determination genes, especially on neuroblast differentiation and yolk protein genes transcription.

mir-279 is a short RNA molecule found in Drosophila melanogaster that belongs to a class of molecules known as microRNAs. microRNAs are ~22nt-long non-coding RNAs that post-transcriptionally regulate the expression of genes, often by binding to the 3' untranslated region of mRNA, targeting the transcript for degradation. miR-279 has diverse tissue-specific functions in the fly, influencing developmental processes related to neurogenesis and oogenesis, as well as behavioral processes related to circadian rhythms. The varied roles of mir-279, both in the developing and adult fly, highlight the utility of microRNAs in regulating unique biological processes.

The gene Maelstrom, Mael, creates a protein, which was first located in Drosophila melanogaster in the nuage perinuclear structure and has functionality analogous to the spindle, spn, gene class. Its mammalian homolog is MAEL.

Norbert Perrimon is a French geneticist and developmental biologist. He is the James Stillman Professor of Developmental Biology in the Department of Genetics at Harvard Medical School, an Investigator at the Howard Hughes Medical Institute, and an Associate of the Broad Institute. He is known for developing a number of techniques for used in genetic research with Drosophila melanogaster, as well as specific substantive contributions to signal transduction, developmental biology and physiology.

<span class="mw-page-title-main">Homologous somatic pairing</span>

Somatic pairing of homologous chromosomes is similar to pre- and early meiotic pairing, and has been observed in Diptera (Drosophila), and budding yeast, for example. Mammals show little pairing apart from in germline cells, taking place at specific loci, and under the control of developmental signalling.

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The somatic mutation and recombination tests (SMARTs) are in vivo genotoxicity tests performed in Drosophila melanogaster (Fruit fly). These fruit fly tests are a short-term test and a non-mammalian approach for in vivo testing of putative genotoxins found in the environment. D. melanogaster has a short lifespan, which allows for fast reproductive cycles and high-throughput genotoxicity testing. D. melanogaster also has around 75% functional orthologs of human disease-related genes, making it an attractive in vivo model for human research. The tests identify loss of heterozygosity for the specified genetic markers in heterozygous or trans-heterozygous adults using phenotypically observable genetic markers in adult tissues. Although diverse events like point mutations/deletions, nondisjunction, and homologous mitotic recombination might theoretically cause this loss of heterozygosity, nondisjunction processes are generally not relevant for most of the examined chemicals. SMARTs are two different tests that use the same genetic foundation, but target different adult tissues and are named accordingly: the wing-spot test and the eye-spot test.

The germ cell nest forms in the ovaries during their development. The nest consists of multiple interconnected oogonia formed by incomplete cell division. The interconnected oogonia are surrounded by somatic cells called granulosa cells. Later on in development, the germ cell nests break down through invasion of granulosa cells. The result is individual oogonia surrounded by a single layer of granulosa cells. There is also a comparative germ cell nest structure in the developing spermatogonia, with interconnected intracellular cytoplasmic bridges.

References

  1. 1 2 3 Whiteley, Mary; Noguchi, Philip D.; Sensabaugh, Suzanne M.; Odenwald, Ward F.; Kassis, Judith A. (1992-02-01). "The Drosophila gene escargot encodes a zinc finger motif found in snail-related genes". Mechanisms of Development. 36 (3): 117–127. doi:10.1016/0925-4773(92)90063-P. ISSN   0925-4773. PMID   1571289. S2CID   23873732.
  2. 1 2 3 4 Korzelius, Jerome; Naumann, Svenja K; Loza-Coll, Mariano A; Chan, Jessica SK; Dutta, Devanjali; Oberheim, Jessica; Gläßer, Christine; Southall, Tony D; Brand, Andrea H; Jones, D Leanne; Edgar, Bruce A (2014-10-08). "Escargotmaintains stemness and suppresses differentiation inDrosophilaintestinal stem cells". The EMBO Journal. 33 (24): 2967–2982. doi:10.15252/embj.201489072. ISSN   0261-4189. PMC   4282643 . PMID   25298397. S2CID   1335408.
  3. Loza-Coll, Mariano A; Southall, Tony D; Sandall, Sharsti L; Brand, Andrea H; Jones, D Leanne (2014-12-17). "Regulation of Drosophila intestinal stem cell maintenance and differentiation by the transcription factor Escargot". EMBO Journal. 33 (24): 2983–2996. doi:10.15252/embj.201489050. ISSN   0261-4189. PMC   4282644 . PMID   25433031.
  4. Kiger, Amy A.; White-Cooper, Helen; Fuller, Margaret T. (2000-10-12). "Somatic support cells restrict germline stem cell self-renewal and promote differentiation". Nature. 407 (6805): 750–754. Bibcode:2000Natur.407..750K. doi:10.1038/35037606. ISSN   1476-4687. PMID   11048722. S2CID   4349276.
  5. Voog, Justin; Sandall, Sharsti L.; Hime, Gary R.; Resende, Luís Pedro F.; Loza-Coll, Mariano; Aslanian, Aaron; Yates, John R.; Hunter, Tony; Fuller, Margaret T.; Jones, D. Leanne (2014-05-08). "Escargot Restricts Niche Cell to Stem Cell Conversion in the Drosophila Testis". Cell Reports. 7 (3): 722–734. doi:10.1016/j.celrep.2014.04.025. ISSN   2211-1247. PMC   4128242 . PMID   24794442.
  6. 1 2 Hayashi, Shigeo; Hirose, Susumu; Metcalfe, Tony; Shirras, Alan D. (1993-05-01). "Control of imaginal cell development by the escargot gene of Drosophila". Development. 118 (1): 105–115. doi:10.1242/dev.118.1.105. ISSN   0950-1991. PMID   8375329.
  7. Ashraf, Shovon I.; Hu, Xiaodi; Roote, John; Ip, Y. Tony (1999-11-15). "The mesoderm determinant Snail collaborates with related zinc-finger proteins to control Drosophila neurogenesis". The EMBO Journal. 18 (22): 6426–6438. doi:10.1093/emboj/18.22.6426. ISSN   0261-4189. PMC   1171705 . PMID   10562554.
  8. Cai, Y. (2001-04-02). "A family of Snail-related zinc finger proteins regulates two distinct and parallel mechanisms that mediate Drosophila neuroblast asymmetric divisions". The EMBO Journal. 20 (7): 1704–1714. doi:10.1093/emboj/20.7.1704. PMC   145473 . PMID   11285234.
  9. Ramat, Anne; Audibert, Agnès; Louvet-Vallée, Sophie; Simon, Françoise; Fichelson, Pierre; Gho, Michel (2016-01-01). "Escargot and Scratch regulate neural commitment by antagonizing Notch-activity inDrosophilasensory organs". Development. 143 (16): 3024–3034. doi: 10.1242/dev.134387 . ISSN   1477-9129. PMID   27471258. S2CID   23382591.
  10. 1 2 Sênos Demarco, Rafael; Stack, Brian J.; Tang, Alexander M.; Voog, Justin; Sandall, Sharsti L.; Southall, Tony D.; Brand, Andrea H.; Jones, D. Leanne (2022-04-19). "Escargot controls somatic stem cell maintenance through the attenuation of the insulin receptor pathway in Drosophila". Cell Reports. 39 (3): 110679. doi:10.1016/j.celrep.2022.110679. ISSN   2211-1247. PMC   9043617 . PMID   35443165.
  11. Miao, Guangxia; Hayashi, Shigeo (2016-01-01). "Escargot controls the sequential specification of two tracheal tip cell types by suppressing FGF signaling inDrosophila". Development. 143 (22): 4261–4271. doi:10.1242/dev.133322. ISSN   1477-9129. PMC   5117212 . PMID   27742749.
  12. 1 2 3 Kerner, Pierre; Hung, Johanne; Béhague, Julien; Le Gouar, Martine; Balavoine, Guillaume; Vervoort, Michel (2009-05-09). "Insights into the evolution of the snail superfamily from metazoan wide molecular phylogenies and expression data in annelids". BMC Evolutionary Biology. 9 (1): 94. Bibcode:2009BMCEE...9...94K. doi: 10.1186/1471-2148-9-94 . ISSN   1471-2148. PMC   2688512 . PMID   19426549.
  13. Manzanares, M; Locascio, A; Nieto, M.A (2001-04-01). "The increasing complexity of the Snail gene superfamily in metazoan evolution". Trends in Genetics. 17 (4): 178–181. doi:10.1016/s0168-9525(01)02232-6. ISSN   0168-9525. PMID   11275308.
  14. Roark, M; Sturtevant, M A; Emery, J; Vaessin, H; Grell, E; Bier, E (1995-10-01). "scratch, a pan-neural gene encoding a zinc finger protein related to snail, promotes neuronal development". Genes & Development. 9 (19): 2384–2398. doi: 10.1101/gad.9.19.2384 . ISSN   0890-9369. PMID   7557390.
  15. Li, Zilan (2022-06-01). Characterization of Larval Lepidopteran Gut Stem Cell Markers (MS thesis). Clemson University. Retrieved 20 January 2024 via All Theses.
  16. Chatterjee, Deeptiman; Cong, Fei; Wang, Xian-Feng; Costa, Caique Almeida Machado; Huang, Yi-Chun; Deng, Wu-Min (2022-12-14). "Cell polarity opposes Jak-STAT mediated Escargot activation that drives intratumor heterogeneity in a Drosophila tumor model". bioRxiv: 2022.12.12.520127. doi:10.1101/2022.12.12.520127. S2CID   254687327.
  17. Yagi, Yoshimasa; Suzuki, Toshiharu; Hayashi, Shigeo (1998-09-15). "Interaction between Drosophila EGF receptor and vnd determines three dorsoventral domains of the neuroectoderm". Development. 125 (18): 3625–3633. doi:10.1242/dev.125.18.3625. ISSN   0950-1991. PMID   9716528.
  18. Fuse, Naoyuki; Hirose, Susumu; Hayashi, Shigeo (1996-04-01). "Determination of wing cell fate by the escargot and snail genes in Drosophila". Development. 122 (4): 1059–1067. doi:10.1242/dev.122.4.1059. ISSN   0950-1991. PMID   8620833.
  19. Fuse, N; Hirose, S; Hayashi, S (1994-10-01). "Diploidy of Drosophila imaginal cells is maintained by a transcriptional repressor encoded by escargot". Genes & Development. 8 (19): 2270–2281. doi: 10.1101/gad.8.19.2270 . ISSN   0890-9369. PMID   7958894. S2CID   8168608.
  20. Rosales-Bravo, Fernando; Sánchez-Díaz, Iván; Reynaud, Enrique; Narváez-Padilla, Verónica (2020-02-11). "Escargot is involved in labial and antennal imaginal disc development through two different developmental pathways". bioRxiv: 2020.02.10.942862. doi:10.1101/2020.02.10.942862. S2CID   214170599.
  21. Hekmat-Scafe, Daria S; Dang, Kim N; Tanouye, Mark A (2005-03-01). "Seizure Suppression by Gain-of-Function escargot Mutations". Genetics. 169 (3): 1477–1493. doi:10.1534/genetics.104.036558. ISSN   1943-2631. PMC   1449553 . PMID   15654097.
  22. Yang, Dong-Jin; Chung, Ji-Youn; Lee, Su-Jin; Park, So-Young; Pyo, Jung-Hoon; Ha, Nam-Chul; Yoo, Mi-Ae; Park, Bum-Joon (2010-07-15). "Slug, mammalian homologue gene of Drosophila escargot, promotes neuronal-differentiation through suppression of HEB/daughterless". Cell Cycle. 9 (14): 2861–2874. doi:10.4161/cc.9.14.12247. ISSN   1538-4101. S2CID   33062924.