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Synthetic Circuits for Multicellular Spatial Patterning


Wang, Sheng (2023) Synthetic Circuits for Multicellular Spatial Patterning. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/3rbk-g805.


Self-organized spatial periodic patterning mechanisms are responsible for the generation of repetitive structures, such as digits, vertebrae, and teeth, during multicellular development. Adopting a synthetic biology approach, we aim to unravel the core principles of multicellular spatial patterning by designing and reconstituting it in tissue-cultured cell lines.

The reaction-diffusion mechanism, as an established paradigm, has successfully elucidated and forecasted pattern formation across varying scales and species. However, the potential for reconstituting synthetic reaction-diffusion patterns using unconventional reaction-diffusion elements within mammalian cell cultures has been insufficiently explored, thus leaving a gap in our comprehension of how spatial periodic patterns could be generated.

The simplest reaction-diffusion systems are thought to necessitate a minimum of two morphogens to generate periodic patterns. In contrast, with the help of mathematical modeling, we illustrate that a simpler circuit, comprising only a single diffusible morphogen, can adequately produce long-range, spatially periodic patterns. These patterns propagate outward from transient initiating perturbations and remain stable after the disturbance is removed. Moreover, introducing an additional bistable intracellular feedback or operation on a growing cell lattice can enhance the robustness of the patterning against noise.

Concurrently, we reconstruct the Turing pattern in mammalian cell culture utilizing a bottom-up approach. We construct a synthetic circuit based on two signaling pathways. After validation of each circuit component, we exhibit the spatial pattern formation driven by a synthetic reaction-diffusion circuit within the mammalian cell line. This adaptable circuit facilitates us to adjust circuit parameters or implement various boundary conditions, thereby revealing the impact of these alterations on patterning dynamics.

Collectively, these findings lay the groundwork for the engineering of pattern formation in the nascent field of synthetic developmental biology.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Synthetic biology; Reaction-diffusion; Spatial patterning; Self-organization
Degree Grantor:California Institute of Technology
Division:Biology and Biological Engineering
Major Option:Bioengineering
Thesis Availability:Restricted to Caltech community only
Research Advisor(s):
  • Elowitz, Michael B.
Thesis Committee:
  • Goentoro, Lea A. (chair)
  • Murray, Richard M.
  • Meister, Markus
  • Elowitz, Michael B.
Defense Date:23 May 2023
Non-Caltech Author Email:aobom2010 (AT)
Record Number:CaltechTHESIS:06022023-192547723
Persistent URL:
Related URLs:
URLURL TypeDescription adapted for Chapter 2
Wang, Sheng0000-0002-4070-7313
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:16061
Deposited By: Sheng Wang
Deposited On:09 Jun 2023 15:11
Last Modified:17 Jun 2024 17:01

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