Biology subjects

Cebria, F.

Publications and source records attributed to Cebria, F..

6 recordsLinked to original sources

bioRxiv2026

Flavins in Focus: Vitamin B2 as a Metabolic Keystone for Neuronal Repair in Regenerating Planarians

Regeneration imposes substantial metabolic demands to support the reconstruction of functional tissues. Essential vitamins are indispensable metabolic cofactors, yet whether their availability is spatially organized to support local metabolic demands within regenerative tissues remains largely unknown. Here, we identify previously undescribed flavin-rich cells, referred to as 'flavinocytes', that form an extensive network that spatially organizes vitamin B2 metabolism in the planarian Schmidtea mediterranea. Using endogenous flavin autofluorescence as a label-free in vivo metabolic readout, we show that this network consists of elongated cells that form longitudinal varicosity-containing strands closely associated with the central nervous system. RNAi-mediated disruption of riboflavin uptake and metabolism reduced flavin-associated autofluorescence and its spatial distribution within the animal, while affecting blastema formation, eye regeneration, and nervous system reconstruction. These findings demonstrate that riboflavin metabolism is required for successful regeneration. Single-cell transcriptomics, protein localization, and functional perturbations further suggest a reciprocal relationship between flavinocytes and the regenerating nervous system, pointing to coordinated neuro-metabolic interactions during tissue repair. Together, our findings demonstrate the importance of riboflavin metabolism for nervous system regeneration and provide new insight into the spatial organization of metabolism during tissue regeneration.

developmental biology↗

bioRxiv2026

A PCTAIRE family kinase regulates eye and brain size in freshwater planarians

BackgroundDuring embryonic development and regeneration, the growth of any organ must be tightly regulated in order to achieve their optimal final size and become fully functional. Freshwater planarians, with their remarkable plasticity and ability to regenerate any part of their body based upon the presence of adult pluripotent stem cells, provide an ideal model to study how the final organ size is regulated during this process. Also, the fact that planarians are constantly growing and degrowing depending on culture conditions, allows us to study how the size of the different organs is determined under homeostatic cell renewal. ResultsHere, we investigate the role of Smed-pctk-1, a cyclin dependent kinase that belongs to the PCTAIRE subfamily of CDKs, which remains largely understudied. Functional analyses show that Smed-pctk-1 silencing disrupts the normal size of the cephalic ganglia and results in an overgrowth of the eyes both in homeostatic and regenerating planarians. The increase in eye size correlates to an increase in the number of both progenitor and differentiated eye cell types. Phototaxis behavioral assays reveal that Smed-pctk-1 RNAi planarians exhibit a precocious sensitivity to light. ConclusionsOverall, our findings identify Smed-pctk-1 as a key regulator of eye and neural size in planarians, highlighting its contribution to the mechanisms that control organ growth during both regeneration and homeostasis.

developmental biology↗

bioRxiv2023

LIM-HD transcription factors are required for regeneration of neuronal and intestinal cell subtypes in planarians

Adult planarians can regenerate the gut, eyes, and even a functional brain in just a few days after injury. Proper regeneration of these complex structures requires that signals guide and restrict the commitment of their adult stem cells and ensure the identity and patterning of the newly formed structures. During embryogenesis of both vertebrates and invertebrates, LIM Homeodomain (LIM-HD) transcription factors act in a combinatorial LIM code that controls crucial aspects of cell fate determination and cell differentiation, including specification of neuronal cell type identity and axonal guidance. So far, however, our understanding about the role these genes may play during regeneration is limited. Here, we report the identification and functional characterization of the full repertoire of LIM-HD genes in Schmidtea mediterranea. We found that these lim homeobox genes (lhx) appear mainly expressed in complementary patterns along the cephalic ganglia and digestive system of the planarian. By functional RNAi based analysis we have identified that several Smed-lhx genes (islet1, lhx1/5-1, lhx2/9-3, lhx6/8, lmx1a/b-2 and lmx1a/b-3) are essential to pattern and size the planarian brain as well as for correct regeneration of specific subpopulations of dopaminergic, serotonergic, GABAergic and cholinergic neurons, while others (Smed-lhx1/5.2 and Smed-lhx2/9.2) are required for the proper expression of diverse intestinal cell type markers, specifically the goblet subtype. LIM-HD are also involved in the control of axonal pathfinding (lhx6/8), axial patterning (islet1 and lmx1a/b-3), head/body proportions (islet2) and stem cell proliferation (lhx3/4, lhx2/9-3, lmx1a/b-2 and lmx1a/b-3) in planarians. Altogether, our results suggest that planarian LIM-HD could provide a combinatorial LIM code to control axial patterning, axonal growing as well as to specify distinct neuronal and intestinal cell identities during regeneration.

developmental biology↗

bioRxiv2020

Planarian CREB-binding protein (CBP) gene family regulates stem cell maintenance and differentiation

The regulation of stem cells plasticity and differentiation is still an open question in developmental biology. CBP (CREB-binding protein)/p300 is a conserved gene family which functions as a transcriptional co-activator and shows an important role in a wide range of cellular processes, such as cell death, DNA damage response and tumorigenesis. Moreover, CBPs have an acetyl transferase activity that is relevant as histone and non-histone acetylation results in changes in chromatin architecture and protein activity that affects gene expression. Many studies have shown the conserved functions of CBP/p300 on stem cell proliferation and differentiation. The planarian Schmidtea mediterranea is an excellent model to study in vivo the molecular mechanism underlying stem cell differentiation during regeneration. We have identified five different Smed-cbp genes in S. mediterranea that show different expression patterns. Functional analyses indicate that Smed-cbp-2 seems to be essential for stem cell maintenance and cell survival. On the other hand, the silencing of Smed-cbp-3 results in the growth of apparently normal blastemas; however, these remain largely depigmented and undifferentiated. Smed-cbp-3 silencing affects the differentiation of several cell lineages including neural, epidermal, digestive and excretory cell types. Finally, we have analyzed the predicted interactomes of CBP-2 and CBP-3 as an initial step to better understand their function on planarian stem cell biology.

developmental biology↗

bioRxiv2019

Hydrogen peroxide as regeneration-initiation signal that activates pERK to trigger planarian regeneration

Despite the extensive research on molecular pathways controlling the process of regeneration in planarians and other regeneration models, little is known about the actual initiation signals necessary to induce regeneration. Previously the involvement of ROS, EGFR and MAPK/ERK has been demonstrated during planarian regeneration, however the exact interplay has not been yet described. By selectively interfering with major mediators in all three key parts (ROS, EGFR & MAPK/ERK), we were able to identify amputation/wound-induced ROS, and H2O2 specifically, as upstream cue in activating regeneration-initiation. In addition, our results demonstrate new relationships between regeneration related ROS production and MAPK/ERK activation at early regeneration stages, as well as the involvement of the EGFR-signaling pathway. In summary, our results suggest a new and more extensive signaling model with ROS, and H2O2, highlighted as upstream initiation-factor and its important functions in the downstream EGFR-MAPK/ERK pathway during planarian regeneration.

developmental biology↗

bioRxiv2018

Smed-egfr-4 is required for planarian eye regeneration

Planarians are amazing animals that can regenerate a whole body from a tiny piece of them thanks to their pluripotent stem cells, the neoblasts. Planarian neoblasts include both pluripotent stem cells and specialized lineage-committed progenitors that give rise to all the mature cell types during regeneration and homeostatic cell turnover in these plastic animals. Little is known, however, about the mechanisms that regulate neoblast differentiation. Recently, it has been shown that Smed-egfr-1, a homologue of the epidermal growth factor receptor (EGFR) family is required for the final differentiation of the gut progenitors into mature cells but not for their specification. As planarians have several EGFR homologues it has been proposed that they could have diverged functionally to regulate the differentiation of the different cell types found in these animals. Here, we report on the function of Smed-egfr-4 on eye regeneration. The silencing of this gene by RNAi results in animals regenerating smaller eyes compared to controls. The numbers of both eye mature cell types, photoreceptor neurons and eye-cup pigment cells, are significantly decreased in the Smed-egfr-4(RNAi) animals. In contrast, the number of eye progenitor cells expressing the specific markers Smed-ovo and Smed-sp6-9 is increased. These results suggest that Smed-egfr-4 would be required not for the specification of eye progenitor cells but rather for their final differentiation and support the idea that in planarians the EGFR pathway could play a general role regulating the differentiation of lineage-committed progenitors.

developmental biology↗