Cytoneme

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Cytonemes take up and transport morphogens. This micrograph shows tissues from a Drosophila larva whose tracheal cells are marked with membrane-tethered mCherry fluorescent protein. Some of the cytonemes that extend from the tracheal branch contact the underlying wing imaginal disc and transport the Dpp morphogen protein (marked with green fluorescent protein) to the tracheal cells. Tracheal cytonemes.jpg
Cytonemes take up and transport morphogens. This micrograph shows tissues from a Drosophila larva whose tracheal cells are marked with membrane-tethered mCherry fluorescent protein. Some of the cytonemes that extend from the tracheal branch contact the underlying wing imaginal disc and transport the Dpp morphogen protein (marked with green fluorescent protein) to the tracheal cells.

Cytonemes are thin, cellular projections that are specialized for exchange of signaling proteins between cells. [1] Cytonemes emanate from cells that make signaling proteins, extending directly to cells that receive signaling proteins. [2] Cytonemes also extend directly from cells that receive signaling proteins to cells that make them. [1] [3] [4]

A cytoneme is a type of filopodium - a thin, tubular extension of a cell’s plasma membrane that has a core composed of tightly bundled, parallel actin filaments. Filopodia can extend more than 100 μm and have been measured as thin as 0.1 μm and as thick as 0.5 μm. Cytonemes with a diameter of approximately 0.2 μm and as long as 80 μm have been observed in the Drosophila wing imaginal disc. [1] The term cytoneme was coined to denote the presence of cytoplasm in their interior (cyto-) and their finger-like appearance (-neme), and to distinguish their role as signaling, rather than structural or force-generating, organelles.[ citation needed ]

Filopodia with behaviors suggestive of roles in sensing patterning information were first observed in sea urchin embryos, [5] and subsequent characterizations support the idea that they convey patterning signals between cells. [6] [7] The discovery of cytonemes in Drosophila imaginal discs [1] correlated for the first time the presence and behavior of filopodia with a known morphogen signaling protein - decapentaplegic. Decapentaplegic is expressed in the wing disc by cells that function as a developmental organizer, [8] [9] and cytonemes that are responsive to decapentaplegic orient toward this developmental organizer. Receptors for signaling proteins are present in motile vesicles in cytonemes, [3] and receptors for different signaling proteins segregate specifically to different types of cytonemes. [4] In Drosophila, cytonemes have been found in wing and eye imaginal discs, [3] [10] trachea, [11] [12] lymph glands [13] and ovaries. [14] They have also been described in spider embryos, [15] earwig ovaries, [16] Rhodnius, [17] Calpodes, [17] earthworms, [18] retroviral-infected cells, [19] mast cells, [20] B-lymphocytes [21] and neutrophils. [22] Recent observations suggest that cytonemes have also an important role during vertebrate development. Recent observations suggest that cytonemes also have an important role during development of the zebrafish neural plate [23] where they transport Wnt8a and of the chick limb where they transport Sonic hedgehog. [24]

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Developmental biology is the study of the process by which animals and plants grow and develop. Developmental biology also encompasses the biology of regeneration, asexual reproduction, metamorphosis, and the growth and differentiation of stem cells in the adult organism.

<i>Drosophila melanogaster</i> Species of fruit fly

Drosophila melanogaster is a species of fly in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly", "pomace fly", or "banana fly". In the wild, D. melanogaster are attracted to rotting fruit and fermenting beverages, and are often found in orchards, kitchens and pubs.

<span class="mw-page-title-main">Sonic hedgehog protein</span> Signaling molecule in animals

Sonic hedgehog protein (SHH) is encoded for by the SHH gene. The protein is named after the video game character Sonic the Hedgehog.

<i>Drosophila</i> embryogenesis Embryogenesis of the fruit fly Drosophila, a popular model system

Drosophila embryogenesis, the process by which Drosophila embryos form, is a favorite model system for genetics and developmental biology. The study of its embryogenesis unlocked the century-long puzzle of how development was controlled, creating the field of evolutionary developmental biology. The small size, short generation time, and large brood size make it ideal for genetic studies. Transparent embryos facilitate developmental studies. Drosophila melanogaster was introduced into the field of genetic experiments by Thomas Hunt Morgan in 1909.

<span class="mw-page-title-main">Morphogen</span> Biological substance that guides development by non-uniform distribution

A morphogen is a substance whose non-uniform distribution governs the pattern of tissue development in the process of morphogenesis or pattern formation, one of the core processes of developmental biology, establishing positions of the various specialized cell types within a tissue. More specifically, a morphogen is a signaling molecule that acts directly on cells to produce specific cellular responses depending on its local concentration.

Hox genes, a subset of homeobox genes, are a group of related genes that specify regions of the body plan of an embryo along the head-tail axis of animals. Hox proteins encode and specify the characteristics of 'position', ensuring that the correct structures form in the correct places of the body. For example, Hox genes in insects specify which appendages form on a segment, and Hox genes in vertebrates specify the types and shape of vertebrae that will form. In segmented animals, Hox proteins thus confer segmental or positional identity, but do not form the actual segments themselves.

<span class="mw-page-title-main">Filopodia</span> Actin projections on the leading edge of lamellipodia of migrating cells

Filopodia are slender cytoplasmic projections that extend beyond the leading edge of lamellipodia in migrating cells. Within the lamellipodium, actin ribs are known as microspikes, and when they extend beyond the lamellipodia, they're known as filopodia. They contain microfilaments cross-linked into bundles by actin-bundling proteins, such as fascin and fimbrin. Filopodia form focal adhesions with the substratum, linking them to the cell surface. Many types of migrating cells display filopodia, which are thought to be involved in both sensation of chemotropic cues, and resulting changes in directed locomotion.

Compartments can be simply defined as separate, different, adjacent cell populations, which upon juxtaposition, create a lineage boundary. This boundary prevents cell movement from cells from different lineages across this barrier, restricting them to their compartment. Subdivisions are established by morphogen gradients and maintained by local cell-cell interactions, providing functional units with domains of different regulatory genes, which give rise to distinct fates. Compartment boundaries are found across species. In the hindbrain of vertebrate embryos, rhombomeres are compartments of common lineage outlined by expression of Hox genes. In invertebrates, the wing imaginal disc of Drosophila provides an excellent model for the study of compartments. Although other tissues, such as the abdomen, and even other imaginal discs are compartmentalized, much of our understanding of key concepts and molecular mechanisms involved in compartment boundaries has been derived from experimentation in the wing disc of the fruit fly.

The Hedgehog signaling pathway is a signaling pathway that transmits information to embryonic cells required for proper cell differentiation. Different parts of the embryo have different concentrations of hedgehog signaling proteins. The pathway also has roles in the adult. Diseases associated with the malfunction of this pathway include cancer.

<span class="mw-page-title-main">Ultrabithorax</span> Protein-coding gene found in Drosophila melanogaster

Ultrabithorax (Ubx) is a homeobox gene found in insects, and is used in the regulation of patterning in morphogenesis. There are many possible products of this gene, which function as transcription factors. Ubx is used in the specification of serially homologous structures, and is used at many levels of developmental hierarchies. In Drosophila melanogaster it is expressed in the third thoracic (T3) and first abdominal (A1) segments and represses wing formation. The Ubx gene regulates the decisions regarding the number of wings and legs the adult flies will have. The developmental role of the Ubx gene is determined by the splicing of its product, which takes place after translation of the gene. The specific splice factors of a particular cell allow the specific regulation of the developmental fate of that cell, by making different splice variants of transcription factors. In D. melanogaster, at least six different isoforms of Ubx exist.

<span class="mw-page-title-main">Mothers against decapentaplegic homolog 1</span> Protein-coding gene in the species Homo sapiens

Mothers against decapentaplegic homolog 1 also known as SMAD family member 1 or SMAD1 is a protein that in humans is encoded by the SMAD1 gene.

Decapentaplegic (Dpp) is a key morphogen involved in the development of the fruit fly Drosophila melanogaster and is the first validated secreted morphogen. It is known to be necessary for the correct patterning and development of the early Drosophila embryo and the fifteen imaginal discs, which are tissues that will become limbs and other organs and structures in the adult fly. It has also been suggested that Dpp plays a role in regulating the growth and size of tissues. Flies with mutations in decapentaplegic fail to form these structures correctly, hence the name. Dpp is the Drosophila homolog of the vertebrate bone morphogenetic proteins (BMPs), which are members of the TGF-β superfamily, a class of proteins that are often associated with their own specific signaling pathway. Studies of Dpp in Drosophila have led to greater understanding of the function and importance of their homologs in vertebrates like humans.

Philip Arden Beachy is Ernest and Amelia Gallo Professor at Stanford University School of Medicine in Palo Alto, California and an Associate at Stanford's Institute of Stem Cell Biology and Regenerative Medicine.

<span class="mw-page-title-main">French flag model</span> Biological model

The French flag model is a conceptual definition of a morphogen, described by Lewis Wolpert in the 1960s. A morphogen is defined as a signaling molecule that acts directly on cells to produce specific cellular responses dependent on morphogen concentration. During early development, morphogen gradients generate different cell types in distinct spatial order. French flag patterning is often found in combination with others: vertebrate limb development is one of the many phenotypes exhibiting French flag patterning overlapped with a complementary pattern.

Orthodenticle (otd) is a homeobox gene found in Drosophila that regulates the development of anterior patterning, with particular involvement in the central nervous system function and eye development. It is located on the X chromosome. The gene is an ortholog of the human OTX1/OTX2 gene.

Skeletogenesis is a key morphogenetic event in the embryonic development of vertebrates and is of equal, although transient, importance in the development of the sea urchin, a marine invertebrate. The larval sea urchin does not resemble its adult form, because the sea urchin is an indirect developer, meaning its larva form must undergo metamorphosis to form the juvenile adult. Here, the focus is on skeletogenesis in the sea urchin species Strongylocentrotus purpuratus, as this species has been most thoroughly studied and characterized.

Philip William Ingham FRS, FMedSci, Hon. FRCP is a British geneticist, currently the Toh Kian Chui Distinguished Professor at the Lee Kong Chian School of Medicine, a partnership between Nanyang Technological University, Singapore and Imperial College, London. Previously, he was the inaugural Director of the Living Systems Institute at the University of Exeter, UK and prior to that was Vice Dean, Research at the Lee Kong Chian School of Medicine.

Dally is the name of a gene that encodes a HS-modified-protein found in the fruit fly. The protein has to be processed after being codified, and in its mature form it is composed by 626 amino acids, forming a proteoglycan rich in heparin sulfate which is anchored to the cell surface via covalent linkage to glycophosphatidylinositol (GPI), so we can define it as a glypican. For its normal biosynthesis it requires sugarless (sgl), a gene that encodes an enzyme which plays a critical role in the process of modification of dally.

<i>Homeotic protein bicoid</i> Protein-coding gene in the species Drosophila melanogaster

Homeotic protein bicoid is encoded by the bcd maternal effect gene in Drosophilia. Homeotic protein bicoid concentration gradient patterns the anterior-posterior (A-P) axis during Drosophila embryogenesis. Bicoid was the first protein demonstrated to act as a morphogen. Although bicoid is important for the development of Drosophila and other higher dipterans, it is absent from most other insects, where its role is accomplished by other genes.

<span class="mw-page-title-main">Gooseberry (gene)</span>

Gooseberry (gsb) is a segment polarity gene located on chromosome 2 of the Drosophila genome. Gooseberry is known for its interactions with key embryonic signaling pathways Wingless and Hedgehog. The gene also has clinical significance, being linked to diseases such as Waardenburg Syndrome and rhabdomyosarcoma.

References

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  2. ↑ Callejo A, Bilioni A, Mollica E, Gorfinkiel N, Andrés G, Ibáñez C, Torroja C, Doglio L, Sierra J, Guerrero I (August 2011). "Dispatched mediates Hedgehog basolateral release to form the long-range morphogenetic gradient in the Drosophila wing disk epithelium". Proceedings of the National Academy of Sciences of the United States of America. 108 (31): 12591–8. Bibcode:2011PNAS..10812591C. doi: 10.1073/pnas.1106881108 . PMC   3150953 . PMID   21690386.
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  10. ↑ Cohen M, Georgiou M, Stevenson NL, Miodownik M, Baum B (July 2010). "Dynamic filopodia transmit intermittent Delta-Notch signaling to drive pattern refinement during lateral inhibition". Developmental Cell. 19 (1): 78–89. doi: 10.1016/j.devcel.2010.06.006 . PMID   20643352.
  11. ↑ Ribeiro C, Ebner A, Affolter M (May 2002). "In vivo imaging reveals different cellular functions for FGF and Dpp signaling in tracheal branching morphogenesis". Developmental Cell. 2 (5): 677–83. doi: 10.1016/S1534-5807(02)00171-5 . PMID   12015974.
  12. ↑ Sato M, Kornberg TB (August 2002). "FGF is an essential mitogen and chemoattractant for the air sacs of the drosophila tracheal system". Developmental Cell. 3 (2): 195–207. doi: 10.1016/S1534-5807(02)00202-2 . PMID   12194851.
  13. ↑ Mandal L, Martinez-Agosto JA, Evans CJ, Hartenstein V, Banerjee U (March 2007). "A Hedgehog- and Antennapedia-dependent niche maintains Drosophila haematopoietic precursors". Nature. 446 (7133): 320–4. Bibcode:2007Natur.446..320M. doi:10.1038/nature05585. PMC   2807630 . PMID   17361183.
  14. ↑ Rojas-Ríos P, Guerrero I, González-Reyes A (2012). "Cytoneme-mediated delivery of hedgehog regulates the expression of bone morphogenetic proteins to maintain germline stem cells in Drosophila". PLOS Biology. 10 (4): e1001298. doi: 10.1371/journal.pbio.1001298 . PMC   3317903 . PMID   22509132.
  15. ↑ Akiyama-Oda Y, Oda H (May 2003). "Early patterning of the spider embryo: a cluster of mesenchymal cells at the cumulus produces Dpp signals received by germ disc epithelial cells". Development. 130 (9): 1735–47. doi: 10.1242/dev.00390 . PMID   12642480.
  16. ↑ Tworzydlo W, Kloc M, Bilinski SM (May 2010). "Female germline stem cell niches of earwigs are structurally simple and different from those of Drosophila melanogaster". Journal of Morphology. 271 (5): 634–40. doi:10.1002/jmor.10824. PMID   20029934. S2CID   28360965.
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  19. ↑ Sherer NM, Lehmann MJ, Jimenez-Soto LF, Horensavitz C, Pypaert M, Mothes W (March 2007). "Retroviruses can establish filopodial bridges for efficient cell-to-cell transmission". Nature Cell Biology. 9 (3): 310–5. doi:10.1038/ncb1544. PMC   2628976 . PMID   17293854.
  20. ↑ Fifadara NH, Beer F, Ono S, Ono SJ (February 2010). "Interaction between activated chemokine receptor 1 and FcepsilonRI at membrane rafts promotes communication and F-actin-rich cytoneme extensions between mast cells". International Immunology. 22 (2): 113–28. doi:10.1093/intimm/dxp118. PMC   2825160 . PMID   20173038.
  21. ↑ Gupta N, DeFranco AL (February 2003). "Visualizing lipid raft dynamics and early signaling events during antigen receptor-mediated B-lymphocyte activation". Molecular Biology of the Cell. 14 (2): 432–44. doi:10.1091/mbc.02-05-0078. PMC   149983 . PMID   12589045.
  22. ↑ Galkina SI, Molotkovsky JG, Ullrich V, Sud'ina GF (April 2005). "Scanning electron microscopy study of neutrophil membrane tubulovesicular extensions (cytonemes) and their role in anchoring, aggregation and phagocytosis. The effect of nitric oxide". Experimental Cell Research. 304 (2): 620–9. doi:10.1016/j.yexcr.2004.12.005. PMID   15748905.
  23. ↑ Stanganello E, Hagemann AI, Mattes B, Sinner C, Meyen D, Weber S, Schug A, Raz E, Scholpp S (January 2015). "Filopodia-based Wnt transport during vertebrate tissue patterning". Nature Communications. 6: 5846. Bibcode:2015NatCo...6.5846S. doi: 10.1038/ncomms6846 . PMID   25556612.
  24. ↑ Sanders TA, Llagostera E, Barna M (May 2013). "Specialized filopodia direct long-range transport of SHH during vertebrate tissue patterning". Nature. 497 (7451): 628–32. Bibcode:2013Natur.497..628S. doi:10.1038/nature12157. PMC   4197975 . PMID   23624372.
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