合成生物学在探索生物图案形成基本原理中的应用与展望

Applications and prospects of synthetic biology in exploring the basic principles of biological pattern formation

自然界中不同生物图案形成的背后是否存在普遍规律,是生物学最基本的科学问题之一。然而,生物系统的复杂性给归纳、理解和验证潜在的普遍规律带来了极大挑战。合成生物学采用自下而上的工程策略,利用功能明确的基因元件构建定量可控的合成体系,为解析生物图案形成的基本原理带来了新的契机。本文围绕合成生物学在生物图案形成研究中的应用,重点阐述了利用合成生物系统验证成形素浓度梯度模型和反应-扩散模型等现有生物图案形成理论的研究进展,并总结了合成生物学在探索生物图案尺寸调控、周期性生物图案形成和多细胞结构产生新机制中的重要贡献。最后提出对合成系统的研究与发育生物学的进一步交互有望拓展对自然生物图案形成的认知,并指出合成生物图案今后在生物材料制造、再生医学和组织工程等领域的应用价值和前景。

Living organisms exhibit amazing spatiotemporal patterns in many traits,such as animal skin,body shapes,etc.Pattern formation is the reliable and recurrent generation of orderly patterns or structures.Whether there is a universal design principle(s)underlying this process remains a fundamental scientific question.Although genetic studies have revealed diverse gene regulatory networks involved in pattern formation,finding unifying principles is usually difficult due to the complexity of biological systems.In parallel,theoretical models that omit biological details but extract the essence of the system have been established.However,verification of these conceptual models in real biological systems is difficult.Through the'bottom-up'construction of synthetic systems with well-characterized genetic parts,synthetic biology provides an effective approach to reveal biological principles in biological pattern formation.In this review,we first give a brief introduction of two major theories of biological pattern formation,the morphogen gradient model and the reaction-diffusion model.Then we review recent synthetic biology studies on biological pattern formation,highlighting its contributions to the validation of existing theories and the discovery of novel pattern formation mechanisms,such as the regulation of scaling,the formation of periodic patterns and the selforganization of multicellular structures.Finally,we envision that the intersection between synthetic biology and developmental biology will inspire researchers to reexamine the natural pattern formation process,where novel mechanisms discovered from synthetic systems may play an important role.We further discuss the possible applications of synthetic pattern-forming systems in biomaterial fabrication,regenerative medicine and tissue engineering in the future.