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The position of the AVE cells (genetically labelled with Hhex-GFP) at the start and end of their migration within the early post-implantation mouse embryo.
The position of the AVE cells (genetically labelled with Hhex-GFP) at the start and end of their migration within the early post-implantation mouse embryo.

A new paper published in Developmental Cell is the result of a collaboration between the Srinivas (Oxford) and Scialdone (Helmholtz Munich) groups. The two teams combined their respective experimental and computational expertise to unravel the molecular characteristics of a unique migratory cell population (the anterior visceral endoderm; AVE) essential for setting up differences along the head-tail axis in mammals.

We all start off as a homogenous collection of cells derived from a fertilised egg. The three anatomical axes (head-tail, front-back, and left-right), much like the Cartesian co-ordinate system defining points within three-dimensional space, provide a framework within which cells exhibit the different behaviours required to ‘sculpt’ a complex organism. Setting up the anatomical axes in a reliable and reproducible manner, is therefore necessary for embryonic development to progress normally.

“Soon after implantation, when the mouse embryo is just a group of few hundred cells, a dozen or so cells, called the AVE, embark on a characteristic migration over a few hours, to a specific location. This location determines which side the head will form. In our study we sought a thorough molecular description of what drives this unique migratory behaviour” says Dr Shifaan Thowfeequ, the Oxford team lead author.

The paper outlines how computational predictions drawn from transcriptomic and phosphoproteomic data were experimentally tested using genetic and pharmacological interventions along with high-resolution lattice lightsheet and confocal time lapse microscopy. The results revealed the tight spatial and temporal coupling of the migratory behaviour with the changing transcriptional landscape, cytoskeletal phosphoproteome and tissue-specific inter-cellular communication pathways. The Semaphorin signalling pathway was one such pathway identified to control the intricacies of AVE migration.

Professor Shankar Srinivas (Oxford) comments "The migration of AVE cells is one of the earliest events that shape our body in the womb. We still understand relatively little about how this stereotypic coordinated movements is achieved. In addition to revealing previously unappreciated molecular players that control this process, this work demonstrates the power of highly interdisciplinary and collaborative team-science in advancing our understanding of fundamental cellular and developmental processes." Antonio Scialdone (Helmholtz Munich) adds “The strength of our study lies in combining multiple data types to demonstrate that intercellular communication and the regulation of cytoskeletal activity contribute to a precise and robust AVE migration. The synergy between computational modelling and experimental validation was crucial in achieving this.”


Read the paper here