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Hezez, T.

Publications and source records attributed to Hezez, T..

2 recordsLinked to original sources

Regeneration of distinct complex structures in the annelid Platynereis is partially based on common morphological, cellular, and molecular events

Many metazoan species harbor fascinating regenerative capabilities, but the underlying mechanisms remain poorly understood. Whether the capacity to regenerate complex structures successfully relies on common or divergent features is still an open question. To identify the key molecular and cellular elements necessary for successful regeneration, we investigated the efficient regeneration of two distinct complex structures in the annelid worm Platynereis dumerilli. By combining classical morphological and developmental approaches, with state-of-the-art single-cell RNA sequencing and analysis, we conducted a comprehensive comparison of locomotory appendage and posterior part regeneration. We uncovered the rich cell type diversity of this Platynereis appendage, over a third of which are nerve-related populations, highlighting the importance of its sensory function. We also described its regenerative process at the morphological and cellular levels, defining stages that include the formation of a proliferative blastema. We then compared posterior part and appendage blastemas, specifically assessing their cell diversity and cell differentiation trajectories. We found transcriptionally similar epithelial and mesodermal progenitors at play during posterior and appendage regeneration, although their specific trajectories differed to some extent. Our work, revealing partial morphological, molecular and cellular parallels between these two efficient regenerations within a single species, sets the foundation for addressing the fundamental question of regeneration success in animals.

developmental biology↗

Dual PAX3/7 transcriptional activities spatially encode spinal cell fates through distinct gene networks

Understanding how transcription factors regulate organized cellular diversity in developing tissues remains a major challenge due to their pleiotropic functions. We addressed this by monitoring and genetically modulating the activity of PAX3 and PAX7 during the specification of neural progenitor pools in the embryonic spinal cord. Using mouse models, we show that the balance between the transcriptional activating and repressing functions of these factors is modulated along the dorsoventral axis and is instructive to the patterning of spinal progenitor pools. By combining loss-of-function experiments with functional genomics in spinal organoids, we demonstrate that PAX-mediated repression and activation rely on distinct cis-regulatory genomic modules. This enables both the coexistence of their dual activity in dorsal cell progenitors and the specific control of two major differentiation programs. PAX promotes H3K27me3 deposition at silencers to repress ventral identities, while at enhancers, they act as pioneer factors, opening and activating cis-regulatory modules to specify dorsal-most identities. Finally, we show that this pioneer activity is restricted to cells exposed to BMP morphogens, ensuring spatial specificity. These findings reveal how PAX proteins, modulated by morphogen gradients, orchestrate neuronal diversity in the spinal cord, providing a robust framework for neural subtype specification.

developmental biology↗