Regulated tissue fluidity steers zebrafish body elongation

Abstract

SUMMARYThe tailbud is the posterior leading edge of the growing vertebrate embryo and consists of motile progenitors of the axial skeleton, musculature and spinal cord. We measure the 3D cell flow field of the zebrafish tailbud and identify changes in tissue fluidity revealed by reductions in the coherence of cell motion without alteration of cell velocities. We find a directed posterior flow wherein the polarization between individual cell motion is high, reflecting ordered collective migration. At the posterior tip of the tailbud, this flow makes sharp bilateral turns facilitated by extensive cell mixing due to increased directional variability of individual cell motions. Inhibition of Wnt or Fgf signaling or cadherin 2 function reduces the coherence of the flow but has different consequences for trunk and tail extension. Modeling and additional data analyses suggest that the balance between the coherence and rate of cell flow determines whether body elongation is linear or whether congestion forms within the flow and the body axis becomes contorted.

FGF and canonical Wnt signaling cooperate to induce paraxial mesoderm from tailbud neuromesodermal progenitors through regulation of a two-step epithelial to mesenchymal transition

“…In the zebrafish tailbud, EMT has been defined primarily by changes in cell movement and morphology (Lawton et al, 2013;Manning and Kimelman, 2015). EMT and EMT-like events during development, homeostasis and metastasis are characterized by expression of the intermediate filament protein vimentin (Lowery et al, 2015).…”

“…Loss of early FGF signaling causes a loss of brachyury expression, leading to defects in mesoderm induction (Ciruna and Rossant, 2001;Griffin et al, 1995;Isaacs et al, 1994;Latinkic et al, 1997). FGF signaling continues to be active in the tailbud, where it plays crucial roles in maintaining the progenitors of the spinal cord (called the neural stem zone), in promoting the proper migration of cells through the tailbud and PM, and in establishing wavefront activity necessary for somitogenesis, although its role in tailbud mesoderm induction from NMPs is unknown (Akai et al, 2005;Dubrulle et al, 2001;Hubaud and Pourquie, 2014;Lawton et al, 2013;Mathis et al, 2001;Steventon et al, 2016). By contrast, canonical Wnt signaling is known to have a conserved essential role during the induction of mesoderm from NMPs (Bouldin et al, 2015;Garriock et al, 2015;Gouti et al, 2014;Henrique et al, 2015;Jurberg et al, 2014;Martin and Kimelman, 2012;Tsakiridis et al, 2014;Wymeersch et al, 2016).…”

“…Several mesoderm-inducing signaling pathways, including canonical Wnt, TGFβ and FGF, promote the gastrula stage mesodermal EMT (Acloque et al, 2009). The study of postgastrula EMT in NMPs has been hampered by the lack of tailbudspecific EMT molecular markers, and has been limited to analysis of cell behaviors in the tailbud (Lawton et al, 2013;Manning and Kimelman, 2015;Steventon et al, 2016). After gastrulation, cells exhibit behavioral changes as they transition from NMP to PM.…”

“…After gastrulation, cells exhibit behavioral changes as they transition from NMP to PM. NMPs exhibit collective epithelial-like migration, whereas the mesoderm derived from NMPs exhibits rapid individual cell migration consistent with mesenchyme (Lawton et al, 2013). In zebrafish, the mesodermal EMT during both gastrulation and later in the tailbud occurs as a two-step process Row et al, 2011).…”

Extracellular matrix motion and early morphogenesis

“…In other words, cellular motility is more diffusive (less persistent) in the posterior part of the PSM compared with the anterior. Similarly, in the zebrafish embryo, increased variability of individual cell velocity has been observed at the posterior tip of the elongating tailbud, suggesting that this motion pattern is conserved among vertebrate species Lawton et al, 2013). These data suggest that the material properties of the ECM in avian PSM might also differ along an anterior-toposterior gradient, with the anteriormost ECM moving more slowly than the posteriormost ECM.…”