Search

Collective cell migration, where cells move as a cohesive unit, is a vital process underlying morphogenesis and cancer metastasis. Thanks to recent advances in imaging and modelling, we are beginning to understand the intricate relationship between a cell and its microenvironment and how this shapes cell polarity, metabolism and modes of migration. The use of biophysical and mathematical models offers a fresh perspective on how cells migrate collectively, either flowing in a fluid-like state or transitioning to more static states. Continuing to unite researchers in biology, physics and mathematics will enable us to decode more complex biological behaviours that underly collective cell migration; only then can we understand how this coordinated movement of cells influences the formation and organisation of tissues and directs the spread of metastatic cancer. In this Perspective, we highlight exciting discoveries, emerging themes and common challenges that have arisen in recent years, and possibleways forward to bridge the gaps in our current understanding of collective cell migration. [ABSTRACT FROM AUTHOR]

Here, we report the generation of a transgenic Lifeact-EGFP quail line for the investigation of actin organization and dynamics during morphogenesis in vivo. This transgenic avian line allows for the high-resolution visualization of actin structures within the living embryo, from the subcellular filaments that guide cell shape to the supracellular assemblies that coordinate movements across tissues. The unique suitability of avian embryos to live imaging facilitates the investigation of previously intractable processes during embryogenesis. Using high-resolution live imaging approaches, we present the dynamic behaviors and morphologies of cellular protrusions in different tissue contexts. Furthermore, through the integration of live imaging with computational segmentation, we visualize cells undergoing apical constriction and large-scale actin structures such as multicellular rosettes within the neuroepithelium. These findings not only enhance our understanding of tissue morphogenesis but also demonstrate the utility of the Lifeact-EGFP transgenic quail as a new model system for live in vivo investigations of the actin cytoskeleton. [ABSTRACT FROM AUTHOR]

The neural crest generates numerous cell types, but conflicting results leave developmental origins unresolved. Here using somatic mosaic variants as cellular barcodes, we infer embryonic clonal dynamics of trunk neural crest, focusing on the sensory and sympathetic ganglia. From three independent adult neurotypical human donors, we identified 1,278 mosaic variants using deep whole-genome sequencing, then profiled allelic fractions in 187 anatomically dissected ganglia. We found a massive rostrocaudal spread of progenitor clones specific to sensory or sympathetic ganglia, which unlike in the brain, showed robust bilateral distributions. Computational modeling suggested neural crest progenitor fate specification preceded delamination from neural tube. Single-cell multiomic analysis suggested both neurons and glia contributed to the rostrocaudal clonal organization. CRISPR barcoding in mice and live imaging in quail embryos confirmed these clonal dynamics across multiple somite levels. Our findings reveal an evolutionarily conserved clonal spread of cells populating peripheral neural ganglia.

Our understanding of how the first mammalian cell lineages arise has been shaped largely by studies of the preimplantation mouse embryo. Painstaking work over many decades has begun to reveal how a single totipotent cell is transformed into a multilayered structure representing the foundations of the body plan. Here, we review how the first lineage decision is initiated by epigenetic regulation but consolidated by the integration of morphological features and transcription factor activity. The establishment of pluripotent and multipotent stem cell lines has enabled deeper analysis of molecular and epigenetic regulation of cell fate decisions. The capability to assemble these stem cells into artificial embryos is an exciting new avenue of research that offers a long-awaited window into cell fate specification in the human embryo. Together, these approaches are poised to profoundly increase our understanding of how the first lineage decisions are made during mammalian embryonic development., (Copyright © 2020 Cold Spring Harbor Laboratory Press; all rights reserved.)