Simple developmental model reveals cell line shapes and links to regeneration

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Various forms of complex multicellular organisms have evolved on Earth, ranging from the simple Volvox carterii which has only 2 cell types to us humans with over 200 cell types. All originate from a single-celled zygote, and their developmental processes depend on the regulation of switch-type genes. These processes have been studied in detail in a few model organisms such as the worm C. elegans, and the fruit fly D. melanogaster. It is also known that the key molecules and mechanisms involved in the development of multicellular organisms are highly conserved across species.

What is also remarkable is that only a handful of molecules and mechanisms that go into the development of a multicellular organism can generate such a diversity of shapes and complexity. Recently, researchers at the Center for Soft and Living Matter at the Institute for Basic Science investigated how this is possible using a simple mathematical model. Through this work, they sought to answer two seemingly opposing questions: what are the limits of diversity that can be generated by development, and what common characteristics are shared among all multicellular organisms during their development.

Three processes are common to biological development in all multicellular organisms: cell division, cell signaling and gene regulation. As such, the model in this study generated millions of these rules and explored them impartially. The maps generated by the model represent how one type of cell transforms into another during the life of the organism. Traditionally, old cell-type maps based on single-celled transcriptomics are biased to resemble a tree, with stem cells located at the root of the tree and increasingly specialized cells appearing downstream along the branches of the tree. ‘tree. However, the cell-type maps produced by the new mathematical model were far from tree-like; it was found that there were many cross-links between different branches of cell types. These resulted in directed acyclic charts, and tree lines were found to be the least common. This means that it is possible that several developmental pathways converge to the terminal cell type in the maps generated by the model.

Surprisingly, it was also found that many organisms produced by the mathematical model were endowed with the ability to regenerate lost cells, without any selection imposed by the authors. When a single cell type is isolated from the adult organism, a single cell can transform and reconstitute all the other cell types. This ability to generate all the cells in the body is called pluripotency, and these cells endow the model organisms with the regenerative capacity of the whole body. Interestingly, most tree lines contained few pluripotent cells, compared to other types of graphs.

While mammals, including humans, are particularly bad at regenerating damaged parts, many animals such as worms and hydras are exceptionally good at this ability. In fact, whole body regeneration occurs largely in the multicellular animal tree of life, and therefore, it has been hypothesized that whole body regeneration could be an epiphenomenon of biological development itself. The fact that pluripotency has occurred in this greatly simplified model suggests that this trait is indeed likely to emerge due to the development process itself, and no special additional components are required to set it up.

In addition to these results, it is expected that the framework of this model can be used to study many other aspects of development. This generative model is simple and modular, and it can be easily extended to explore important processes that were not included in the present study, such as the effect of the spatial arrangement of cells and the effect of cell death. . The researchers further described some possible real-life experiments to test some of the predictions made by their mathematical model. It is hoped that the framework of this model will prove useful in discovering new features of development, which may have a wide range of implications in developmental biology and regenerative medicine.

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