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Single-cell approaches and deep learning to map all stages of fruit fly embryo development

Scientists have constructed the most complete and detailed single-cell map of embryo development in any animalto date, using the fruit fly as a model organism.

Published in Science, this study, co-led by Eileen Furlong at EMBL and Jay Shendure at the University of Washington, harnesses data from over one million embryonic cells spanning all stages of embryo development and represents a significant advance at multiple levels. This fundamental research also aids scientists’ ability to pursue questions like how mutations lead to different developmental defects. In addition, it provides a path to understand the vast non-coding part of our genome that contains most disease-associated mutations.

“Just capturing the entirety of embryogenesis — all stages and all cell types — to obtain a more complete view of the cell states and molecular changes that accompany development is a feat in its own right,” said Eileen Furlong, Head of EMBL’s Genome Biology unit. “But what I’m really excited about is the use of deep learning to obtain a continuous view of the molecular changes driving embryonic development — down to the minute.”

Embryonic development begins with the fertilisation of an egg, followed by a series of cell divisions and decisions that give rise to a very complex multi-cellular embryo that can move, eat, sense, and interact with its environment. Researchers have been studying this process of embryonic development for over a hundred years, but only in the last decade have new technologies enabled scientists to identify molecular changes that accompany cell transitions at a single-cell level.

These single-cell studies have raised tremendous excitement as they demonstrated the complexity of cell types in tissues, even identifying new cell types, and revealed their developmental trajectories in addition to underlying molecular changes. However, attempts to profile the entirety of embryo development at single-cell resolution have been out of reach due to many technical challenges in sampling, costs, and technologies.

In this regard, the fruit fly (Drosophila melanogaster), a pre-eminent model organism in developmental biology, gene regulation, and chromatin biology, has some key advantages when it comes to developing new approaches to address this. Fruit fly embryonic development occurs extremely rapidly; within just 20 hours after fertilisation, all tissues have formed, including the brain, gut, and heart, so the organism can crawl and eat. This, in combination with the many discoveries made in fruit flies that have propelled understanding of how genes and their products work, encouraged the Furlong lab and their collaborators to take on this challenge.

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