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Kardash, E.

Publications and source records attributed to Kardash, E..

2 recordsLinked to original sources

Quantification of cell behaviours and computational modelling show that cell directional behaviours drive zebrafish pectoral fin morphogenesis

MotivationUnderstanding the mechanisms by which the zebrafish pectoral fin develops is expected to produce insights on how vertebrate limbs grow from a 2D cell layer to a 3D structure. Two mechanisms have been proposed to drive limb morphogenesis in tetrapods: a growth-based morphogenesis with a higher proliferation rate at the distal tip of the limb bud than at the proximal side, and directed cell behaviors that include elongation, division and migration in a nonrandom manner. Based on quantitative experimental biological data at the level of individual cells in the whole developing organ, we test the conditions for the dynamics of pectoral fin early morphogenesis. ResultsWe found that during the development of the zebrafish pectoral fin, cells have a preferential elongation axis that gradually aligns along the proximodistal axis (PD) of the organ. Based on these quantitative observations, we build a center-based cell model enhanced with a polarity term and cell proliferation to simulate fin growth. Our simulations resulted in 3D fins similar in shape to the observed ones, suggesting that the existence of a preferential axis of cell polarization is essential to drive fin morphogenesis in zebrafish, as observed in the development of limbs in the mouse, but distal tip-based expansion is not. AvailabilityUpon publication, biological data will be available at http://bioemergences.eu/modelingFin, and code source at https://github.com/guijoe/MaSoFin. Contactjoel.dokmegang-kassap@stu.mmu.ac.uk, nadine.peyrieras@cnrs.fr or rene.doursat@iscpif.fr Supplementary informationSupplementary data are included in this manuscript.

systems biology↗

A contractile acto-myosin belt promotes growth anisotropy during the early stages of pectoral fin development in zebrafish.

The zebrafish pectoral fin is an in vivo model for vertebrate limb formation, well suited to investigate the integration of molecular and cellular dynamics, the results of which translate into shaping the limb bud. We used the ratio between the lengths of the anterior-posterior (AP) and dorso-ventral (DV) axes as the descriptor of how fin shape changes over time. We showed that fin shape transitions from close to hemi-spherical (ratio 1. 36 {+/-} 0.11) to semi-ellipsoid (ratio 1.64 {+/-} 0.04) between 33 and 46 hours post fertilization (hpf). This shape transition coincided with the formation of a contractile \"actin belt\" at the distal rim of the fin bud along its AP axis. The actin belt emerged from a central position and expanded on both sides along the distal rim of the fin, thus marking the DV boundary between two rows of ectodermal cells. Formation of the actin belt depended on Rac protein activity, as suggested by FRET measurements using a Rac biosensor. 3D+time imaging of the developing fin in Rac-deficient embryos showed that anisotropic growth of the fin depends on the actin belt. Indeed, actin belt formation was dramatically reduced or even absent in the embryos without proper Rac activity. This correlated with isotropic growth of the fin bud from normal shape at 33 hpf to quasi hemispherical shape with AP/DV ratio ~1 13 hours later, without affecting cell number and overall bud volume. We propose that the formation of a contractile acto-myosin belt is essential to drive the pectoral fins early anisotropic growth.

developmental biology↗