Biology subjects

Ferenc, J.

Publications and source records attributed to Ferenc, J..

4 recordsLinked to original sources

bioRxiv2024

A transcription factor toggle switch determines differentiated epidermal cell identities in Hydra

In Hydra, a simple cnidarian model, epithelio-muscular cells play a crucial role in shaping and maintaining the body architecture. These cells are continuously renewed as undifferentiated cells from the bodys mid-region get displaced toward the extremities, replacing shed, differentiated cells and adopting specific identities. This ongoing differentiation, coupled with the maintenance of distinct anatomical regions, provides an ideal system to explore the relationship between cell type specification and axial patterning. However, the molecular mechanisms governing epithelial cell identity in Hydra remain largely unknown. In this study, we describe a double-negative feedback loop between the transcription factors Zic4 and Gata3 that functions as a toggle switch to control epidermal cell fate. Zic4 is activated by Wnt signaling from the mouth organizer and triggers battery cell specification in tentacles. In contrast, Gata3 promotes basal disk cell identity at the aboral end. Functional analyses demonstrate that Zic4 and Gata3 are mutually antagonistic; suppression of one leads to the dominance of the other, and vice versa, resulting in ectopic cell specification. Notably, simultaneous knockdown of both factors rescues the phenotype, indicating that it is the balance between these transcription factors, rather than their absolute levels, that dictates cell identity. This study highlights the mechanisms by which distinct cellular identities are established at Hydra body termini and reveals how cell fate decisions are coordinated with axial patterning.

developmental biology↗

bioRxiv2024

Mechanochemical Patterning Localizes the Organizer of a Luminal Epithelium

The spontaneous emergence of tissue patterns is often attributed to biochemical reaction-diffusion systems. In Hydra tissue regeneration, the formation of a Wnt signaling center serves as a well-known example of such a process. However, despite extensive research, a strictly biochemical mechanism for self-organization in Hydra remains elusive. In this study, we investigated mechanical stimuli and identified a positive feedback loop between Wnt signaling and tissue stretching. We developed a mathematical model of mechanochemical pattern formation in a closed elastic shell, representing regenerating Hydra epithelial spheroids. Our model explains how mechanical forces drive axis formation and predicts the organizers location under various perturbations, providing a more comprehensive understanding of the spatial dynamics involved. Validation by partially confining regenerating tissues showed that the organizer indeed forms in regions with the greatest stretching potential. This work highlights a novel mechanochemical mechanism for luminal epithelium patterning, suggesting that mechanical forces, in addition to biochemical signals, play a crucial role in tissue regeneration and axis specification. Our findings offer broader implications for the role of mechanical forces in tissue organization in various biological systems, opening new avenues for investigating mechanochemical feedback in development and regeneration.

developmental biology↗

bioRxiv2021

The transcription factor Zic4 acts as a transdifferentiation switch

The molecular mechanisms that maintain cell identities and prevent transdifferentiation remain mysterious. Interestingly, both dedifferentiation and transdifferentiation are transiently reshuffled during regeneration. Therefore, organisms that regenerate readily offer a fruitful paradigm to investigate the regulation of cell fate stability. Here, we used Hydra as a model system and show that Zic4 silencing is sufficient to induce transdifferentiation of tentacle into foot cells. We identified a Wnt-controlled Gene Regulatory Network that controls a transcriptional switch of cell identity. Furthermore, we show that this switch also controls the re-entry into the cell cycle. Our data indicate that maintenance of cell fate by a Wnt-controlled GRN is a key mechanism during both homeostasis and regeneration. One-Sentence SummaryA Wnt-controlled GRN controls fate maintenance in Hydra.

developmental biology↗

bioRxiv2020

Wnt3 expression as a readout of tissue stretching during Hydra regeneration

Mechanical forces shape cell fate decisions during development and regeneration in many systems. Epithelial lumen volume changes, for example, generate mechanical forces that can be perceived by the surrounding tissue and integrated into cell fate decisions. Similar behavior occurs in regenerating Hydra tissue spheroids, where periodic osmotically driven inflation and deflation cycles generate mechanical stimuli in the form of tissue stretching. Using this model, we investigate how such mechanical input guides the de novo formation of differentiated body parts. We show that the expression of the organizer-defining factor Wnt3 functions as a quantitative readout of cellular stretching and, when supplied externally, enables successful regeneration without mechanical stimulation. This finding represents a previously undescribed cellular mechanism for converting mechanical stimuli to a biochemical signaling readout and guiding cell fate transitions. It also elucidates the role of mechanical oscillations in Hydra regeneration, which long remained unclear. The presence the Wnt/mechanics interplay in Hydra and its relatives underscores the ancient evolutionary history of this crosstalk, possibly extending back to the first metazoans. Since Wnt signaling crosstalks with cellular mechanics in various developmental and disease contexts, it can also represent a conserved feature of this signaling pathway.

developmental biology↗