Cellular and Molecular Mechanisms of Single and Collective Cell Migrations in Drosophila: Themes and Variations

Abstract

The process of cell migration is essential throughout life, driving embryonic morphogenesis and ensuring homeostasis in adults. Defects in cell migration are a major cause of human disease, with excessive migration causing autoimmune diseases and cancer metastasis, whereas reduced capacity for migration leads to birth defects and immunodeficiencies. Myriad studies in vitro have established a consensus view that cell migrations require cell polarization, Rho GTPase-mediated cytoskeletal rearrangements, and myosin-mediated contractility. However, in vivo studies later revealed a more complex picture, including the discovery that cells migrate not only as single units but also as clusters, strands, and sheets. In particular, the role of E-Cadherin in cell motility appears to be more complex than previously appreciated. Here, we discuss recent advances achieved by combining the plethora of genetic tools available to the Drosophila geneticist with live imaging and biophysical techniques. Finally, we discuss the emerging themes such studies have revealed and ponder the puzzles that remain to be solved.

Limits to the precision of gradient sensing with spatial communication and temporal integration

“…The linear noise approximation is applicable in this case. The FDT relates the power spectrum S rr nn′ ðωÞ (fluctuations) to the imaginary part of the generalized susceptibility G nn′ ðωÞ (dissipation), S rr nn′ ðωÞ = 2 ω Im½G nn′ ðωÞ , [7] where G nn′ ðωÞ describes how the receptor binding relaxes to small changes in the free energy,…”

“…Cells are even more sensitive when they are in a group: Cultures of many neurons respond to chemical gradients equivalent to a difference of only one molecule across an individual neuron's axonal growth cone (2), clusters of malignant lymphocytes have a wider chemotactic sensitivity than single cells (3), and groups of communicating epithelial cells detect gradients that are too weak for a single cell to detect (4). More generally, collective chemosensing properties are often very distinct from those in individual cells (3,(5)(6)(7). These observations have generated a renewed interest in the question of what sets the fundamental limit to the precision of gradient sensing in large, spatially extended, often collective sensory systems.…”

Modeling and analysis of collective cell migration in an in vivo three-dimensional environment

“…Even when a signal can be detected, it reveals the bulk of the chemical, whereas the protein that is available for the migrating cell to sense may be a tiny, invisible fraction of the total (13). Moreover, in vivo, cells probably integrate information from multiple signals (6,14), both biochemical and physical. Both the signal and the response may be quite different in 3D in vivo environments compared with 2D experimental paradigms.…”

Segmentation and Shape Analysis of Macrophages Using Anglegram Analysis

“…Macrophages are one of the cells within the immune system that settle in lymphoid tissues and the liver, serving as filters for trapping microbes and foreign particles [1]. Cell migration is an essential biological process that ensures homeostasis in adults, where an unbalanced migratory response results in human disease; with excessive migration causing autoimmune diseases and cancer metastasis [3]. The model organism Drosophila melanogaster can offer insights into how macrophages integrate cues to migration and other tasks [2].…”