Data-Theoretical Synthesis of the Early Developmental Process


Biological development is often described as a dynamic, emergent process. This is evident across a variety of phenomena, from the temporal organization of cell types in the embryo to compounding trends that affect large-scale differentiation. To better understand this, we propose combining quantitative investigations of biological development with theory-building techniques. This provides an alternative to the gene-centric view of development: namely, the view that developmental genes and their expression determine the complexity of the developmental phenotype. Using the model system Caenorhabditis elegans, we examine time-dependent properties of the embryonic phenotype and utilize the unique life-history properties to demonstrate how these emergent properties can be linked together by data analysis and theory-building. We also focus on embryogenetic differentiation processes, and how terminally-differentiated cells contribute to structure and function of the adult phenotype. Examining embryogenetic dynamics from 200 to 400 min post-fertilization provides basic quantitative information on developmental tempo and process. To summarize, theory construction techniques are summarized and proposed as a way to rigorously interpret our data. Our proposed approach to a formal data representation that can provide critical links across life-history, anatomy and function.

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We would like to acknowledge feedback from the OpenWorm and DevoWorm communities, particularly Drs. Stephen Larson, George Mikhailovsky, and senior contributors at the OpenWorm Foundation.

Author information




Manuscript was written by B.A., and revised by R.G. and T.E.P. Figures and tables were created and assembled by B.A., with input from R.G. Analysis was conducted by B.A. Ideas and conception for manuscript were done by B.A., R.G., and T.E.P. Data archival was done by B.A.

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Correspondence to Bradly Alicea.

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Supplementary Information

Supplemental Figure 1

A comparison of developmental and terminally-differentiated cell counts for 50-min intervals. Data collected from embryos raised at 25 °C. (PNG 31 kb)

Supplemental Figure 2

The number of developmental cells alive for each sublineage (AB, MS, C, D, and E) at 20 min time intervals for 200–400 min of embryogenesis. Panel A shows AB and MS, while panel B shows C, D, and E. Data collected from embryos raised at 25 °C. (PNG 116 kb)

Supplemental Figure 3

Heat map showing the emergence of terminally differentiated cells in C. elegans from 200 to 400 min of embryogenesis. Emergence of Terminally Differentiated Cells in each cell type class, relative to the 400 min of embryogenesis. The 200 to 300 min period is sampled at 5-min intervals, while the 300 to 400 min period is sampled at 30-min intervals. Bottom of the figure is labeled with the corresponding developmental stages and images of the embryo during select times. Data collected from embryos raised at 25 °C. (PNG 681 kb)

Supplemental Figure 4

Histogram containing counts of types of cells born during a specific time interval (bins of size 10 except where noted). Figure 5A: Interneurons (blue) vs. Neurons (red), Fig. 5B: Interneurons (blue) vs. Hypodermal cells (red). Gray region denotes bins of size 50. Data collected from embryos raised at 25 °C. (PNG 47 kb)

Supplemental Figure 5

Information content for each terminally-differentiated cell family, based on a hierarchical clustering analysis. Information content (blue bars, left axis) is compared to the number of cells in each family (red bars, right axis). Data collected from embryos raised at 25 °C. (PNG 26 kb)

Supplemental Figure 6

A time-series of CAST coefficients for 200 to 400 min of C. elegans embryogenesis. Time intervals from 200 to 300 min are five minutes in length; time intervals from 300 to 400 min are fifty minutes in length (denoted within gray region). Data collected from embryos raised at 25 °C. (PNG 85 kb)

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Supplemental File 1

Terminally-differentiated cell nomenclature identities and annotations by developmental birth time (min). (XLSX 121 kb)

Supplemental File 2

Table of number of cells born at a specific developmental birth time sampling point (min) for five distinct somatic cell types. (XLSX 8 kb)

Supplemental File 3

Table of somatic cell types by family, class, and developmental birth time (min). (XLSX 24 kb)

Supplemental File 4

Table of cell families by number of family members and average developmental birth time (min). (XLSX 12 kb)

Supplemental File 5

Pairwise alignments (per pairs of birth time sampling points) and calculation of alignment scores for CAST analysis. (XLSX 152 kb)

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Alicea, B., Gordon, R. & Portegys, T.E. Data-Theoretical Synthesis of the Early Developmental Process. Neuroinform (2021).

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  • Developmental biology
  • Computational biology
  • Data science
  • Theoretical models
  • Caenorhabditis elegans