Data-Theoretical Synthesis of the Early Developmental Process

Abstract

Biological development is often described as a dynamic, emergent process. Yet beyond the observation of gene expression in individual cells, it is hard to conceptualize large-scale patterns that confirm this description. We provide an example of combining theoretical insights with a data science approach. The availability of quantitative data allows us to examine aggregate trends across development, from the spatial organization of embryo cells to the temporal trends as they differentiate. The first half of this paper lays out alternatives to the gene-centric view of development: namely, the view that developmental genes and their expression determine the complexity of the developmental phenotype. Caenorhabditis elegans biology provides us with a highly-deterministic developmental cell lineage and clear linkage between zygote and cells of the adult phenotype. These properties allow us to examine time-dependent properties of the embryonic phenotype. We utilize the unique life-history properties of C. elegans to demonstrate how these emergent properties can be linked together by relational processes and data analysis. The second half of this paper focuses on the process of developmental cell terminal differentiation, and how terminally-differentiated cells contribute to structure and function of the adult phenotype. An analysis is conducted for cells that were present during discrete time intervals covering 200 to 400 minutes of embryogenesis, providing us with basic statistics on the tempo of the process in addition to the appearance of specific cell types and their order relative to developmental time. As with ideas presented in the first section, these data may also provide clues as to the timing for the initial onset of stereotyped and autonomic behaviors of the developing animal. Taken together, these overlapping approaches can provide critical links across life-history, anatomy and function.

Computational modeling and analysis of the morphogenetic domain signaling networks regulating C. elegans embryogenesis

“…The key to better understanding the coordination of cellular differentiation in development is to look at the differential transcription within and between cells [16] , [17] , [54] . We proposed the reference virtual embryo model integrated with the spatiotemporal gene expression profile.…”

Periodicity in the embryo: Emergence of order in space, diffusion of order in time

“…One way to generalize our result to a broader cross-species context is to examine related phenomena such as mitotic bookmarking [41], in which heritable regulatory information is transmitted from mother to daughter cells in a cell lineage. Our approach is also quite valuable [see 42,43] for understanding this particular scale of the biological organism. For a fuller understanding in the context of groups of cells producing mean behaviors, we can appeal to the quantal mitosis hypothesis.…”