Abstract
Tissue morphogenesis relies on repeated use of dynamic behaviors at the levels of intracellular structures, individual cells, and cell groups. Rapidly accumulating live imaging datasets make it increasingly important to formalize and automate the task of mapping recurrent dynamic behaviors (motifs), as it is done in speech recognition and other data mining applications. Here, we present a “template-based search” approach for accurate mapping of sub- to multi-cellular morphogenetic motifs using a time series data mining framework. We formulated the task of motif mapping as a subsequence matching problem and solved it using dynamic time warping, while relying on high throughput graph-theoretic algorithms for efficient exploration of the search space. This formulation allows our algorithm to accurately identify the complete duration of each instance and automatically label different stages throughout its progress, such as cell cycle phases during cell division. To illustrate our approach, we mapped cell intercalations during germband extension in the early Drosophila embryo. Our framework enabled statistical analysis of intercalary cell behaviors in wild-type and mutant embryos, comparison of temporal dynamics in contracting and growing junctions in different genotypes, and the identification of a novel mode of iterative cell intercalation. Our formulation of tissue morphogenesis using time series opens new avenues for systematic decomposition of tissue morphogenesis.
Highlights
The formation of functional structures during animal development is governed by repeated use of highly conserved morphogenetic behaviors, such as convergence-extension movements and out-of-plane epithelial deformations [1,2,3,4]
Much like many ballet dances that are choreographed by combining the same movements in different ways, tissue morphogenesis relies on combinations of highly conserved sub- to multi-cellular behaviors, or motifs, such as cell division, death and intercalation
Rather than relying on a set of manually-crafted criteria, our algorithm identifies instances of the motif based on similarity to a user-provided example or template
Summary
The formation of functional structures during animal development is governed by repeated use of highly conserved morphogenetic behaviors, such as convergence-extension movements and out-of-plane epithelial deformations [1,2,3,4]. Several aspects of mesoderm invagination in Drosophila embryos bear striking resemblance to optic cup formation in vertebrates, and both of these processes depend on spatiotemporal modulation of apical cell constriction [5,6] Another example of a highly conserved morphogenetic behavior is provided by Drosophila germband extension, which results in an in-plane reshaping of a patterned epithelial sheet [7]. This convergence-extension process is orchestrated by contractile actomyosin cables that induce directed cell rearrangements, similar to what was observed during vertebrate neurulation [8]. Morphogenetic processes appear to be assembled from commonly used morphogenetic motifs, including apical cell constrictions, cell intercalations, delaminations, collective divisions, and migrations [12,13,14,15,16,17]
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