ReviewCell migration in invertebrates: clues from border and distal tip cells
Introduction
During development, inflammation, angiogenesis and wound repair, cells migrate in response to extracellular signals such as long-range secreted factors and cell matrix bound proteins. For cells to migrate correctly, a number of processes have to be perfectly controlled and orchestrated. Attractant or repellant guidance cues expressed by target tissues have to direct the motile cells along the migratory path. The migrating cell most likely encounters only a slight gradient of the guidance signals. The signal must, therefore, be recognized by a sensitive receptor signaling pathway and amplified into a directed migratory response. The mechanisms of cell migration have been studied mainly in tissue culture assays, which permit the analysis of cell behavior in a controlled environment. Genetic analysis of cell migration has identified genetic pathways that control migratory behavior in the context of whole organisms.
In this review, I focus on the genetic analysis of cell migration in two invertebrate model systems: distal tip cell (DTC) migration in the nematode worm Caenorhabditis elegans and border cell migration in the fruit fly Drosophila melanogaster. Many different aspects of the migration process can be addressed with the analysis of these two migratory systems. The complicated migratory paths of border cells and distal tip cells provide an elegant system to explore how cell migration can be guided within the spatial and temporal context of the organism. (For recent reviews on the genetic analysis of other migrating cells in Drosophila and C. elegans, see 1., 2., 3., 4..)
Section snippets
Border cell migration in Drosophila
Border cells originate at the anterior pole of the developing egg chamber as a group of 6–10 somatic cells. They are part of the follicular epithelium that surrounds the germline cyst and are recruited by the polar cells (5., 6.; Fig. 1a). During a 5–6 hour period, border cells move as a cluster and invade the germline-derived nurse cells (Fig. 1b,c). When the border cells delaminate from the follicle cell layer, they undergo an epithelial→mesenchymal transition and extend large F-actin-filled
Distal tip cell migration in C. elegans
The gonad of the C. elegans hermaphrodite consists of two arms. A single DTC at the tip of each arm controls the development and the shape of each arm (Fig. 2). DTCs are born during the first larval instar in the midbody region, and migrate in three phases (Fig. 2). In the first phase, one DTC moves anteriorly and the other posteriorly along the ventral body wall muscles (Fig. 2a); in the second phase, each DTC turns 90 degrees and moves from the ventral to the dorsal muscle (Fig. 2b); in the
Conclusions and future directions
Border cells and DTCs are only two of the migratory cell populations studied in detail in C. elegans and Drosophila. Other migratory systems include the migration of tracheal and germ cells in Drosophila, and the migration of specific neuroblasts and myoblasts in C. elegans (see 1., 2., 3., 4.). As genetic analysis starts with the identification of mutants displaying an aberrant migratory phenotype, there is no preconception of the type of molecule or even the aspect of the migration affected.
Acknowledgements
I would like to thank members of my lab for encouraging and engaging discussion and members of the Drosophila and C. elegans community for helpful comments. The NIH and the Howard Hughes Medical Institute supports the research in our laboratory.
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
• of special interest
•• of outstanding interest
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The dosage-dependent effect exerted by the NM23-H1/H2 homolog NDK-1 on distal tip cell migration in C. elegans
2018, Laboratory InvestigationRegulating distal tip cell migration in space and time
2017, Mechanisms of DevelopmentCitation Excerpt :Cell migration is essential for proper embryonic development, morphogenesis, immunity, wound healing and regeneration, and inappropriate cell migration can lead to devastating diseases such as metastatic cancer. Mechanisms that regulate cell migration are highly conserved (Heasman and Ridley, 2008; Lehmann, 2001), therefore, studying cell migration in model organisms can yield key insights. The distal tip cells (DTCs) in the nematode C. elegans are an advantageous in vivo model for the study of cell migration.
The spectraplakins of Caenorhabditis elegans: Cytoskeletal crosslinkers and beyond
2017, Seminars in Cell and Developmental BiologyCitation Excerpt :During larva development, the two DTCs lead gonad arms to elongate along the ventral side of the worm body in opposite directions, and then make two turns to continue extending along the dorsal side of the body towards the midline, eventually forming a pair of U-shaped symmetrical gonad arms [46] (Fig. 2C). The movement of the DTCs is closely associated with development timing and can be observed clearly, making DTC migration an ideal model for exploring the basic mechanisms of cell migration during tubular morphogenesis [46–48]. vab-10 was initially identified as a gene essential for DTC migration through a genome-wide RNAi screen approach [49].
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