Abstract

The establishment of precise, high-resolution temporal sequences for morphogenetic events in laboratory mice remains a vexing issue in developmental biology. Mouse embryos collected at the same period of gestation, even those from the same litter, show wide variation in individual levels of progress along their developmental trajectory. Therefore, age at harvest does not provide sufficient information about developmental progress to serve as the basis for forming samples for the study of rapidly or near-simultaneously occurring events such as the sequence of ossification center formation. Here, we generate two measures of individual developmental progress (developmental age) for a large sample of mouse embryos using crown–rump lengths that measures size, and limbstaging ages produced by the embryonic Mouse Ontogenetic Staging System (eMOSS) that measure shape. Using these measures, we establish fine-grained sequences of ossification center appearance for mouse embryos. The two measures of developmental progress generate slightly different sequences of ossification center formation demonstrating that despite their tight correlation throughout the developmental period, size and shape are aspects of form that are at least partially dissociated in development.

Highlights

  • The establishment of precise, high-resolution temporal sequences for morphogenetic events in laboratory mice, currently the most extensively used experimental mammal for studying human development and disease, remains a vexing issue in developmental biology

  • We examine the difference in sequences of ossification center appearance in mouse embryos using these two systems

  • Unravelling the complex nature of sequential and causally-linked events such as gene expression and cellular differentiation is crucial to understanding the developmental processes that comprise morphogenesis

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Summary

Introduction

The establishment of precise, high-resolution temporal sequences for morphogenetic events in laboratory mice, currently the most extensively used experimental mammal for studying human development and disease, remains a vexing issue in developmental biology. One of the main obstacles to establishing a precise developmental timeline for any developmental event is the high level of variability in developmental progress exhibited by embryos collected at similar days of gestation. Mouse embryos collected at the same embryonic age, even littermates, show disparities in morphological progress indicating variation in the rate of development [1,2,3]. For any given developmental process (e.g., palate elevation, heart septation, limb bud development, organogenesis, etc.), each mouse within a litter will exhibit a different amount of progress along the trajectory towards completion of that process. Inter-individual differences in rates of development make it difficult to select individuals

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