Cytonemes are cellular structures recognized for their role in cell communication. These specialized extensions provide a direct means for cells to interact, influencing various biological processes.
Understanding Cytonemes
Cytonemes are slender, dynamic protrusions extending from a cell’s plasma membrane, characterized by a core of tightly bundled actin filaments. These structures are a specific type of filopodia, which are thin, finger-like extensions cells use to explore their environment. Cytonemes have diameters ranging from 0.1 to 0.5 micrometers and can extend over long distances, often over 100 micrometers.
The term “cytoneme” highlights their cytoplasmic content and thread-like appearance, distinguishing them by their specialized signaling function. While filopodia can serve various roles, cytonemes are defined by their capacity to exchange signaling proteins between cells. Their discovery in Drosophila imaginal discs linked the presence of such filopodia directly to the movement of a known signaling protein, Decapentaplegic (Dpp).
The Role of Cytonemes in Cellular Signaling
The primary function of cytonemes is to facilitate precise, direct cell-to-cell communication, acting as conduits for specific signaling molecules. These molecules, known as morphogens or growth factors, are transported along cytonemes to reach target cells. This mechanism ensures highly localized and regulated signal transmission, differing from broader diffusion.
Cytonemes can extend from cells that produce signaling proteins to cells that receive them, and sometimes from receiving cells back to producing cells. For instance, in Drosophila, cytonemes extend from tracheal cells to contact the underlying wing imaginal disc, transporting the Dpp morphogen protein. This direct contact allows for the efficient transfer of signals, often at specialized junctions, termed “cytoneme synapses” due to their similarity to neuronal synapses.
Receptors for signaling proteins are found in mobile vesicles within cytonemes, and different receptors are segregated to different types of cytonemes. This segregation suggests a high level of specificity in cytoneme-mediated signaling, ensuring that particular signals are delivered to the appropriate target cells. Examples of signaling molecules transported by cytonemes include Notch, Epidermal Growth Factor (EGF), Fibroblast Growth Factor (FGF), Bone Morphogenetic Protein (BMP), Wingless (Wnt), and Hedgehog (Hh).
Cytonemes in Development and Disease
Cytonemes play a role in embryonic development and disease. In embryonic development, they guide tissue patterning and organ formation by mediating the precise delivery of morphogens. For example, in Drosophila, cytonemes are involved in establishing the Hedgehog (Hh) gradient and the Decapentaplegic (Dpp) gradient in the wing disc, both important for proper tissue patterning.
Beyond insects, cytonemes have been observed in vertebrate development, including in zebrafish, where they transport Wnt8a in the neural plate, and in chick limbs, where they facilitate Sonic Hedgehog (Shh) transport. These structures ensure that cells receive the correct positional information, influencing cell differentiation and the overall organization of developing tissues. Cytonemes also contribute to asymmetric cell division, impacting the fate of daughter cells by asymmetrically localizing signaling molecules.
In disease, cytonemes are involved in cancer progression and viral spread. Brain tumor cells in glioblastoma can extend ultralong membrane protrusions, sometimes called tumor microtubes, which contribute to invasion, proliferation, and resistance to treatments. In Drosophila tumor models, cytoneme formation is necessary for tumor cells to receive signals from neighboring cells, and inhibiting cytonemes can suppress tumor growth and improve survival. They may also contribute to the survival, invasion, and metastasis of gastrointestinal cancer cells.