Collective durotaxis along a self-generated stiffness gradient in vivo

• Published in: Nature (London) 2021-12, Vol.600 (7890), p.690-694
• Main Authors: Shellard, Adam, Mayor, Roberto
• Format: Article
• Language: English
• Subjects: 14; 631/136; 631/80; Ablation; Actomyosin; Actomyosin - metabolism; Animals; Cadherins; Cell adhesion & migration; Cell migration; Cell Movement; Cell Polarity; Cell research; Chemotaxis; Contractility; Embryos; Female; Hardness; Humanities and Social Sciences; Hypotheses; Mechanical stimuli; Morphogenesis; multidisciplinary; N-Cadherin; Neural crest; Neural Crest - cytology; Pliability; rac GTP-Binding Proteins - metabolism; Science; Science (multidisciplinary); Stiffness; Substrates; Wound healing; Xenopus laevis - embryology
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-021-04210-x

Collective cell migration underlies morphogenesis, wound healing and cancer invasion 1 , 2 . Most directed migration in vivo has been attributed to chemotaxis, whereby cells follow a chemical gradient 3 – 5 . Cells can also follow a stiffness gradient in vitro, a process called durotaxis 3 , 4 , 6 – 8 , but evidence for durotaxis in vivo is lacking 6 . Here we show that in Xenopus laevis  the neural crest—an embryonic cell population—self-generates a stiffness gradient in the adjacent placodal tissue, and follows this gradient by durotaxis. The gradient moves with the neural crest, which is continually pursuing a retreating region of high substrate stiffness. Mechanistically, the neural crest induces the gradient due to N-cadherin interactions with the placodes and senses the gradient through cell–matrix adhesions, resulting in polarized Rac activity and actomyosin contractility, which coordinates durotaxis. Durotaxis synergizes with chemotaxis, cooperatively polarizing actomyosin machinery of the cell group to prompt efficient directional collective cell migration in vivo. These results show that durotaxis and dynamic stiffness gradients exist in vivo, and gradients of chemical and mechanical signals cooperate to achieve efficient directional cell migration. The neural crest of Xenopus laevis self-generates a stiffness gradient in the adjacent placodal tissue and follows this gradient by durotaxis.