Biology subjects

Benazeraf, B.

Publications and source records attributed to Benazeraf, B..

4 recordsLinked to original sources

bioRxiv2024

Differential proliferation regulates multi-tissue morphogenesis during embryonic axial extension: Integrating viscous modeling and experimental approaches.

The study of how mechanical interactions and different cellular behaviors affect tissues and embryo shaping has been and remains an important challenge in biology. Axial extension is a morphogenetic process that results in the acquisition of the elongated shape of the vertebrate embryonic body. Several adjacent tissues are involved in the process, including the tissues that form the spinal cord and musculoskeletal system: the neural tube and the paraxial mesoderm, respectively. Although we have a growing understanding of how each of these tissues elongates, we still need to fully understand the morphogenetic consequences of their growth and mechanical interactions. In this study, we develop a 2D multi-tissue continuum-based mathematical model to simulate and study how differential growth, tissue biophysical properties, and mechanical interactions affect the morphogenesis of the embryonic body during axial extension. Our model captures the long-term dynamics of embryonic posterior tissues previously observed in vivo by time-lapse imaging of bird embryos. It reveals the underestimated influence of differential tissue proliferation rates in inter-tissue interaction and shaping by capturing the relative impact of this process on tissue dynamics. We verified the predictions of our model in quail embryos by showing that decreasing the rate of cell proliferation in the paraxial mesoderm affects long-term tissue dynamics and shaping of both the paraxial mesoderm and the neighboring neural tube. Overall, our work provides a new theoretical platform to consider the long-term consequences of tissue differential growth and mechanical interactions on morphogenesis.

developmental biology↗

bioRxiv2020

Cell-to-cell heterogeneity in Sox2 and Brachyury expression guides progenitor destiny by controllingtheir movements.

Although cell-to-cell heterogeneity in gene and protein expression within cell populations has been widely documented, we know little about its potential biological functions. We addressed this issue by studying progenitors that populate the posterior region of the vertebrate embryos, a cell population known for its capacity to self-renew or to contribute to the formation of the neural tube and paraxial mesoderm tissues. Posterior progenitors are characterized by the co-expression of Sox2 and Brachyury (Bra), two transcription factors related to neural and mesodermal lineages, respectively. In this study, we show that the respective levels of Sox2 and Bra proteins display a high degree of variability among posterior progenitors of the quail embryo. By developing forced expression and downregulation approaches, we further provide evidence that the value of the Sox2-to-Bra ratio in a given progenitor directs its choice of staying in place or exit the progenitor zone to generate neural or mesodermal cells. Time-lapse imaging together with mathematical modeling then reveal that variations of the Sox2-to-Bra ratio confer these cells heterogeneous motile behaviors. While high Bra levels display high motile properties that push cells to join the mesoderm, high levels of Sox2 tend to inhibit cell movement making cells get integrated into the neural tube. Our work thus provides evidence that the spatial heterogeneity of posterior progenitors, with regards to their relative contents of Sox2 and Bra and thus to their motile properties, is fundamental to maintain a pool of resident progenitors while others segregate to contribute to tissue formation. More broadly, our work reveals that heterogeneity among a population of progenitor cells is critical to ensure robust multi-tissue morphogenesis.

developmental biology↗

bioRxiv2020

Cell intercalation driven by SMAD3 underlies secondary neural tube formation

Body axis elongation is a hallmark of the vertebrate embryo, involving the architectural remodelling of the tailbud. Although it is clear how bi-potential neuro-mesodermal progenitors (NMPs) contribute to embryo elongation, the dynamic events that lead to de novo lumen formation and that culminate in the formation of a 3-Dimensional, secondary neural tube from NMPs, are poorly understood. Here, we used in vivo imaging of the chicken embryo to show that cell intercalation downstream of TGF-beta/SMAD3 signalling is required for secondary neural tube formation. Our analysis describes the initial events in embryo elongation including lineage restriction, the epithelial-to-mesenchymal transition of NMPs, and the initiation of lumen formation. Importantly, we show that the resolution of a single, centrally positioned continuous lumen, which occurs through the intercalation of central cells, requires SMAD3 activity. We anticipate that these findings will be relevant to understand caudal, skin-covered neural tube defects, amongst the most frequent birth defects detected in humans. HIGHLIGHTS.- Initiation of the lumen formation follows the acquisition of neural identity and epithelial polarization. .- Programmed cell death is not required for lumen resolution. .- Resolution of a single central lumen requires cell intercalation, driven by Smad3 activity .- The outcome of central cell division preceding cell intercalation, varies along the cranio-caudal axis.

developmental biology↗

bioRxiv2018

Mechanical Coupling Coordinates the Co-elongation of Axial and Paraxial Tissues in Avian Embryos

Tissues undergoing morphogenesis impose mechanical effects on one another. How developmental programs adapt to or take advantage of these effects remains poorly explored. Here, using a combination of live imaging, modeling, and microsurgical perturbations, we show that the axial and paraxial tissues in the forming avian embryonic body coordinate their rates of elongation through mechanical interactions. First, a cell motility gradient drives paraxial presomitic mesoderm (PSM) expansion, resulting in compression of the axial neural tube and notochord; second, elongation of axial tissues driven by PSM compression and polarized cell intercalation pushes the caudal progenitor domain posteriorly; finally, the axial push drives progenitors to emigrate into the PSM to maintain tissue growth and cell motility. These interactions form an engine-like positive feedback loop, which ensures the tissue-coupling and self-sustaining characteristics of body elongation. Our results suggest a general role of inter-tissue forces in the coordination of complex morphogenesis involving distinct tissues.

developmental biology↗