Bioengineering Self-organizing Signalling Centres to Control Embryoid Body Pattern Elaboration

Fokion Glykofrydis, Elise Cachat, Ieva Berzanskyte, Elaine Dzierzak, Jamie A Davies

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Multicellular systems possess an intrinsic capacity to autonomously generate nonrandom state distributions or morphologies in a process termed self-organization. Facets of self-organization, such as pattern formation, pattern elaboration, and symmetry breaking, are frequently observed in developing embryos. Artificial stem cell-derived structures including embryoid bodies (EBs), gastruloids, and organoids also demonstrate self-organization, but with a limited capacity compared to their in vivo developmental counterparts. There is a pressing need for better tools to allow user-defined control over self-organization in these stem cell-derived structures. Here, we employ synthetic biology to establish an efficient platform for the generation of self-organizing coaggregates, in which HEK-293 cells overexpressing P-cadherin (Cdh3) spontaneously form cell clusters attached mostly to one or two locations on the exterior of EBs. These Cdh3-expressing HEK cells, when further engineered to produce functional mouse WNT3A, evoke polarized and gradual Wnt/β-catenin pathway activation in EBs during coaggregation cultures. The localized WNT3A provision induces nascent mesoderm specification within regions of the EB close to the Cdh3-Wnt3a-expressing HEK source, resulting in pattern elaboration and symmetry breaking within EBs. This synthetic biology-based approach puts us closer toward engineering synthetic organizers to improve the realism in stem cell-derived structures.
Original languageEnglish
Pages (from-to)1465–1480
Number of pages16
JournalACS Synthetic Biology
Issue number6
Early online date21 May 2021
Publication statusPublished - 18 Jun 2021

Keywords / Materials (for Non-textual outputs)

  • self-organization
  • patterning
  • symmetry breaking
  • synthetic biology
  • Wnt3a
  • embryoid body


Dive into the research topics of 'Bioengineering Self-organizing Signalling Centres to Control Embryoid Body Pattern Elaboration'. Together they form a unique fingerprint.

Cite this