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An integrated approach identifies the molecular underpinnings of murine anterior visceral endoderm migration.
Dev. Cell, DOI: 10.1016/j.devcel.2024.05.014 (2024)
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.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Anterior Visceral Endoderm ; Cell Migration ; Embryonic Patterning ; Mouse Embryogenesis ; Phosphoproteomics ; Semaphorin Signaling ; Single-cell Transcriptomics
ISSN (print) / ISBN
1534-5807
e-ISSN
1878-1551
Zeitschrift
Developmental Cell
Verlag
Elsevier
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed