Abstract
Goosecoid (Gsc) expression marks the primary embryonic organizer in vertebrates and beyond. While functions have been assigned during later embryogenesis, the role of Gsc in the organizer has remained enigmatic. Using conditional gain-of-function approaches in Xenopus and mouse to maintain Gsc expression in the organizer and along the axial midline, neural tube closure defects (NTDs) arose and dorsal extension was compromised. Both phenotypes represent convergent extension (CE) defects, arising from impaired Wnt/planar cell polarity (PCP) signaling. Dvl2 recruitment to the cell membrane was inhibited by Gsc in Xenopus animal cap assays and key Wnt/PCP factors (RhoA, Vangl2, Prickle, Wnt11) rescued Gsc-mediated NTDs. Re-evaluation of endogenous Gsc functions in MO-mediated gene knockdown frog and knockout mouse embryos unearthed PCP/CE-related phenotypes as well, including cartilage defects in Xenopus and misalignment of inner ear hair cells in mouse. Our results assign a novel function to Gsc as an inhibitor of Wnt/PCP-mediated CE. We propose that in the organizer Gsc represses CE as well: Gsc-expressing prechordal cells, which leave the organizer first, migrate and do not undergo CE like the Gsc-negative notochordal cells, which subsequently emerge from the organizer. In this model, Gsc provides a switch between cell migration and CE, i.e. cell intercalation.
Highlights
During development, invertebrate and vertebrate embryos alike elongate and narrow their anterior-posterior (AP) axis by convergent extension (CE)
Gsc expression in the organizer ceases with the exit of the first cell population, which migrates anteriorly and constitutes the prechordal mesoderm
Our hypothesis predicts that a sustained activity of Gsc along the subsequently emerging notochord interferes with the cellular behavior of these cells, namely CE
Summary
Invertebrate and vertebrate embryos alike elongate and narrow their anterior-posterior (AP) axis by convergent extension (CE). Upon ectopic expression on the ventral side, i.e. opposite to its normal site of action, Gsc efficiently induces the formation of secondary embryonic axes in Xenopus[7]. This remarkable ability to mimic Spemann’s organizer in gain-of-function experiments is readily explained by its well characterized ability to transcriptionally repress target genes identified in mouse, frog and zebrafish, including Wnt8a and BMP4 pathway components[8,9,10,11,12,13,14,15,16,17,18]. Segregation of organizer-derived cells into these two cell populations is accompanied by differences in cell behavior and gene expression: Gsc marks the prechordal cells, characterized by single cell migration, while Brachyury is expressed and instrumental for CE in the notochord[28,29,30,31]
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