Heterotypic contact inhibition of locomotion can drive cell sorting between epithelial and mesenchymal cell populations

TY - JOUR

T1 - Heterotypic contact inhibition of locomotion can drive cell sorting between epithelial and mesenchymal cell populations

AU - Brayford, Simon

AU - Kenny, Fiona Nuala

AU - Hiratsuka, Toru

AU - Serna Morales, Eduardo

AU - Yolland, Lawrence

AU - Luchici, Andrei

AU - Stramer, Brian Marc

PY - 2019/5/10

Y1 - 2019/5/10

N2 - Interactions between different cell-types can induce distinct contact inhibition of locomotion (CIL) responses that are hypothesised to control population-wide behaviours during embryogenesis. However, our understanding of the signals that lead to cell-type specific repulsion and the precise capacity of heterotypic CIL responses to drive emergent behaviours is lacking. Using a new model of heterotypic CIL, we show that fibrosarcoma cells, but not fibroblasts, are actively repelled by epithelial cells in culture. We show that knocking down EphB2 or ERK in fibrosarcoma cells specifically leads to disruption of the repulsion phase of CIL in response to interactions with epithelial cells. We also examine the population-wide effects when these various cell combinations are allowed to interact in culture. Unlike fibroblasts, fibrosarcoma cells completely segregate from epithelial cells and inhibiting their distinct CIL response by knocking down EphB2 or ERK also disrupts this emergent sorting behaviour. These data suggest that heterotypic CIL responses, in conjunction with processes such as differential adhesion, may aid the sorting of cell populations.

AB - Interactions between different cell-types can induce distinct contact inhibition of locomotion (CIL) responses that are hypothesised to control population-wide behaviours during embryogenesis. However, our understanding of the signals that lead to cell-type specific repulsion and the precise capacity of heterotypic CIL responses to drive emergent behaviours is lacking. Using a new model of heterotypic CIL, we show that fibrosarcoma cells, but not fibroblasts, are actively repelled by epithelial cells in culture. We show that knocking down EphB2 or ERK in fibrosarcoma cells specifically leads to disruption of the repulsion phase of CIL in response to interactions with epithelial cells. We also examine the population-wide effects when these various cell combinations are allowed to interact in culture. Unlike fibroblasts, fibrosarcoma cells completely segregate from epithelial cells and inhibiting their distinct CIL response by knocking down EphB2 or ERK also disrupts this emergent sorting behaviour. These data suggest that heterotypic CIL responses, in conjunction with processes such as differential adhesion, may aid the sorting of cell populations.

KW - Cell sorting

KW - Contact inhibition of locomotion

KW - Ephrin signalling

KW - ERK signalling

KW - MAPK signalling

UR - http://www.scopus.com/inward/record.url?scp=85066494074&partnerID=8YFLogxK

U2 - 10.1242/jcs.223974

DO - 10.1242/jcs.223974

M3 - Article

SN - 0021-9533

VL - 132

JO - Journal of Cell Science

JF - Journal of Cell Science

IS - 11

M1 - jcs223974

ER -