Extracellular Vesicles and Membrane Protrusions in Developmental Signaling

Abstract

During embryonic development, cells communicate with each other to determine cell fate, guide migration, and shape morphogenesis. While the relevant secreted factors and their downstream target genes have been characterized extensively, how these signals travel between embryonic cells is still emerging. Evidence is accumulating that extracellular vesicles (EVs), which are well defined in cell culture and cancer, offer a crucial means of communication in embryos. Moreover, the release and/or reception of EVs is often facilitated by fine cellular protrusions, which have a history of study in development. However, due in part to the complexities of identifying fragile nanometer-scale extracellular structures within the three-dimensional embryonic environment, the nomenclature of developmental EVs and protrusions can be ambiguous, confounding progress. In this review, we provide a robust guide to categorizing these structures in order to enable comparisons between developmental systems and stages. Then, we discuss existing evidence supporting a role for EVs and fine cellular protrusions throughout development.

High-resolution 3D ultrastructural analysis of developing mouse neocortex reveals long slender processes of endothelial cells that enter neural cells

“…It is intriguing that the vesicles surrounding the ETC process tip often cluster at the cell extremity (like the apical chimeric protrusions in the ventricle shown in Figure 3 ) in an advantageous position for the formation of extracellular particles. A large variety of extracellular vesicles have been identified in recent years, which can convey important signaling functions ( Holm et al, 2018 ; Gustafson and Gammill, 2022 ; Jeppesen et al, 2023 ). It is conceivable that the vesicle clusters described here form a novel variant of one of these extracellular particle classes—a question that requires further investigation.…”

Olesya Gusachenko

“…As with any other quickly evolving field, exosomederived technology faces many challenges, especially in scaling, standardization, and safety control of exosome manufacturing and its compliance with good manufacturing practices 43,50 . An increasing body of scientific evidence indicates tremendous heterogenicity of exosomes as a group 51 , and a major part of the biology and the functional essence of this diversity remains to be investigated. With multiple small and big companies all over the world jumping into the exosome innovation studies, and startups emerging to specifically target exosomes for medical use the technology is rushing forward, sometimes preceding the science.…”

Emerging roles of prominin-1 (CD133) in the dynamics of plasma membrane architecture and cell signaling pathways in health and disease

“…Exosomes are of endosomal origin, as they are formed by the inward budding of endosome-limiting membranes, leading to the formation of MVBs that subsequently fuse with the plasma membrane and discharge their small intralumenal vesicles into the extracellular medium [ 271 , 274 ]. In contrast, MVs are derived directly from the plasma membrane as they often bud or shed from protruding membranes (reviewed in Refs [ 275 – 277 ]). Depending on the cell type, CD133 has been associated with exosomes or MVs [ 81 , 191 ].…”