Convergent extension: using collective cell migration and cell intercalation to shape embryos

M. Tada; C.-P. Heisenberg

doi:10.1242/dev.073007

Stretch-induced endogenous electric fields drive neural crest directed collective cell migration in vivo

10.1101/2021.10.11.463916 ◽

2021 ◽

Author(s):

Fernando Ferreira ◽

Sofia Moreira ◽

Elias H Barriga

Keyword(s):

Cell Migration ◽

Neural Crest ◽

Electric Fields ◽

Embryonic Cell ◽

Collective Cell Migration ◽

Convergent Extension ◽

Topological Features ◽

Stretch Activated Channels

Directed collective cell migration (dCCM) is essential for morphogenesis. Cell clusters migrate in inherently complex in vivo environments composed of chemical, electrical, mechanical as well as topological features. While these environmental factors have been shown to allow dCCM in vitro, our understanding of dCCM in vivo is mostly limited to chemical guidance. Thus, despite its wide biological relevance, the mechanisms that guide dCCM in vivo remain unclear. To address this, we study endogenous electric fields in relation to the migratory environment of the Xenopus laevis cephalic neural crest, an embryonic cell population that collectively and directionally migrates in vivo. Combining bioelectrical, biomechanical and molecular tools, we show that endogenous electric fields drive neural crest dCCM via electrotaxis in vivo. Moreover, we identify the voltage-sensitive phosphatase 1 (Vsp1) as a key component of the molecular mechanism used by neural crest cells to transduce electric fields into a directional cue. Furthermore, Vsp1 function is specifically required for electrotaxis, being dispensable for cell motility and chemotaxis. Finally, we reveal that endogenous electric fields are mechanoelectrically established. Mechanistically, convergent extension movements of the neural fold generate membrane tension, which in turn opens stretch-activated channels to mobilise the ions required to fuel electric fields. Overall, our results reveal a mechanism of cell guidance, where electrotaxis emerges from the mechanoelectrical and molecular interplay between neighbouring tissues. More broadly, our data contribute to validate the, otherwise understudied, functions of endogenous bioelectrical stimuli in morphogenetic processes.

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Emergence of single cell mechanical behavior and polarity within epithelial monolayers drives collective cell migration

10.1101/2019.12.16.875567 ◽

2019 ◽

Author(s):

Shreyansh Jain ◽

Victoire M.L. Cachoux ◽

Gautham H.N.S. Narayana ◽

Simon de Beco ◽

Joseph D’Alessandro ◽

...

Keyword(s):

Cell Migration ◽

Single Cell ◽

Large Scale ◽

Cancer Metastasis ◽

Cell Junctions ◽

Collective Cell Migration ◽

Convergent Extension ◽

Cell Dynamics

The directed migration of cell collectives is essential in various physiological processes, such as epiboly, intestinal epithelial turnover, and convergent extension during morphogenesis as well as during pathological events like wound healing and cancer metastasis1,2. Collective cell migration leads to the emergence of coordinated movements over multiple cells. Our current understanding emphasizes that these movements are mainly driven by large-scale transmission of signals through adherens junctions3,4. In this study, we show that collective movements of epithelial cells can be triggered by polarity signals at the single cell level through the establishment of coordinated lamellipodial protrusions. We designed a minimalistic model system to generate one-dimensional epithelial trains confined in ring shaped patterns that recapitulate rotational movements observed in vitro in cellular monolayers and in vivo in genitalia or follicular cell rotation5–7. Using our system, we demonstrated that cells follow coordinated rotational movements after the establishment of directed Rac1-dependent polarity over the entire monolayer. Our experimental and numerical approaches show that the maintenance of coordinated migration requires the acquisition of a front-back polarity within each single cell but does not require the maintenance of cell-cell junctions. Taken together, these unexpected findings demonstrate that collective cell dynamics in closed environments as observed in multiple in vitro and in vivo situations5,6,8,9 can arise from single cell behavior through a sustained memory of cell polarity.

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