1. An integrated approach identifies the molecular underpinnings of murine anterior visceral endoderm migration.
- Author
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Thowfeequ S, Fiorentino J, Hu D, Solovey M, Ruane S, Whitehead M, Zhou F, Godwin J, Mateo-Otero Y, Vanhaesebroeck B, Scialdone A, and Srinivas S
- Subjects
- Animals, Mice, Signal Transduction, Semaphorins metabolism, Semaphorins genetics, Embryo, Mammalian metabolism, Embryo, Mammalian cytology, Viscera metabolism, Viscera embryology, Body Patterning genetics, Endoderm metabolism, Endoderm cytology, Cell Movement, Gene Expression Regulation, Developmental
- Abstract
The anterior visceral endoderm (AVE) differs from the surrounding visceral endoderm (VE) in its migratory behavior and ability to restrict primitive streak formation to the opposite side of the mouse embryo. To characterize the molecular bases for the unique properties of the AVE, we combined single-cell RNA sequencing of the VE prior to and during AVE migration with phosphoproteomics, high-resolution live-imaging, and short-term lineage labeling and intervention. This identified the transient nature of the AVE with attenuation of "anteriorizing" gene expression as cells migrate and the emergence of heterogeneities in transcriptional states relative to the AVE's position. Using cell communication analysis, we identified the requirement of semaphorin signaling for normal AVE migration. Lattice light-sheet microscopy showed that Sema6D mutants have abnormalities in basal projections and migration speed. These findings point to a tight coupling between transcriptional state and position of the AVE and identify molecular controllers of AVE migration., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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