Biology subjects

Prieto, D.

Publications and source records attributed to Prieto, D..

8 recordsLinked to original sources

bioRxiv2026

A filopodia-based dendritic mechanosensory compartment in CSF-contacting neurons

Cerebrospinal fluid-contacting neurons (CSF-cNs) are spinal sensory cells that detect chemical and mechanical stimuli via PKD2L1 channels located on a primary cilium, as established in aquatic vertebrates like zebrafish. The mechanosensory mechanism in mammals, however, has remained unclear due to the absence of definitive evidence for cilia on their apical processes (ApPrs). Here we show that mouse CSF-cN ApPrs lack cilia but instead possess drebrin-stabilized filopodia enriched with F-actin. Mechanical stimulation of these cilia-free ApPrs elicits robust, PKD2L1-dependent inward currents, that are sufficient to drive neuronal firing, confirming a novel, cilia-independent mechanosensory mechanism. Comparative analyses indicate an evolutionary divergence from ciliary mechanotransduction, with mice adopting a direct, actin-associated mechanism. These findings advance our understanding of the cellular basis of spinal mechanosensation in mammals and reveal a specialized adaptation for monitoring central canal dynamics, with implications for spinal sensory integration and evolution. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/713694v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@f74408org.highwire.dtl.DTLVardef@193866forg.highwire.dtl.DTLVardef@5f1baaorg.highwire.dtl.DTLVardef@113c3e_HPS_FORMAT_FIGEXP M_FIG C_FIG In BriefCerebrospinal fluid-contacting neurons detect mechanical forces in the spinal cord. In zebrafish, they use a cane-like cilium. Whether mammals inherited this mechanism is controversial. Here, researchers show that mice have replaced the cilium with filopodia, hair-like, touch-sensitive projections stabilized by the protein drebrin. This evolutionary innovation reveals how sensory cells adapt their machinery to the demands of different body plans and environments. HIGHLIGHTS- Mouse spinal CSF-cN apical processes lack cilia. - Drebrin-stabilized filopodia replace the ancestral cilium. - Direct mechanical stimulation of ApPrs evokes PKD2L1-dependent currents and firing. - Mammalian CSF-cNs evolved a cilia-independent mechanosensory mechanism.

neuroscience↗

bioRxiv2026

Connexins are essential for the contribution of latent progenitors to self-repair after spinal cord injury

Gap junctions are important regulators of the biology of neural stem cells. Both in vertebrates with regenerative abilities and neonatal rodents, ependymal cells communicate via connexin (Cx) 43 and Cx26. Gap junction coupling and Cx26 are down-regulated as the ependyma becomes quiescent in adulthood, but injury overrules this developmental down-regulation suggesting a role for Cx signalling in the reactivation of ependymal cells. Here, we aim to explore the role of Cx26 and Cx43 in the response of ependymal cells to injury. We find that Cx26 is critical for the proliferative response to injury and thereby scar formation. Cx43 plays a key role in the communication between ependymal cells of Ca2+ signals induced by activation of P2X7 receptors that trigger downstream events. Our data show that Cxs are relevant targets to manipulate the ependymal stem cell niche to achieve a better self-repair after spinal cord injury.

neuroscience↗

bioRxiv2025

PH sensitivity of cerebrospinal fluid-contacting neurons involves the modulation of phasic and tonic currents mediated by PKD2L1 channels located in the apical process.

Cerebrospinal fluid contacting neurons (CSFcNs) are GABAergic cells that surround the central canal (cc) of the spinal cord. Their soma is located sub-ependymally and they have a dendritic-like process that ends as a bulb (the so-called "apical process"; ApPr) inside the cc. It remains unclear how this unique anatomical organization, with the soma and the ApPr located in different extracellular environments, relates to their function as a multimodal sensor of cerebrospinal fluid (CSF) composition. One of the main physiological features of CSFcNs is a prominent spontaneous electrical activity mediated by PKD2L1 channels, a non-selective cation channel of the TRP family. PKD2L1 channels have a high single-channel conductance (around 200 pS) and can be modulated by protons and mechanical forces. In this work we investigate PKD2L1 channel sensitivity to pH and its effects on CSFcNs excitability. We demonstrate that PKD2L1 spontaneous activity generates not only phasic inward currents, but also a sustained current, both of which are modulated bidirectionally by pH with a high sensitivity around physiological values. By combining electrophysiology (direct recordings from intact and isolated ApPrs) with optical methods (laser-photolysis of protons) we further show that functional PKD2L1 channels are specifically localized in the ApPr. The spatial segregation of PKD2L1 channels, along with their biophysical properties (high single-channel conductance and pH sensitivity) and the ApPrs unique membrane properties (very high input resistance) renders CSFcN excitability exquisitely sensitive to PKD2L1 modulation. Altogether, our findings illustrate how the ApPrs properties are finely tuned to support its sensory role.

neuroscience↗

bioRxiv2025

Disruption of hemocyte differentiation and distribution in Drosophila Ptr23c mutants

In Drosophila, hemocytes are essential for development and immunity, with their differentiation and spatial distribution under strict regulation. Here, we examine the effect of the Ptr23c null mutation in embryonic hemocyte development. Contrary to our initial hypothesis, Ptr does not regulate hemocyte number, as the mutation did not affect the total number of hemocytes, apoptosis, mitosis, or the balance between major subpopulations. However, Ptr23c mutants displayed disrupted distribution and premature hemocyte differentiation, marked by accelerated maturation at stage 12. Despite this early differentiation, Ptr23c embryos exhibited a 50% reduction in mature hemocytes by stage 16, as quantified by serpent-driven mCherry expression. Our findings establish Ptr as a regulator of hemocyte distribution and differentiation timing during normal embryogenesis, possibly through modulation of the serpent pathway.

developmental biology↗

bioRxiv2024

Atypical soluble guanylyl cyclases control brain size in Drosophila

Hypoxia-induced proliferation of neural stem cells has a crucial role in brain development. In the brain of Drosophila melanogaster, the optic lobe exhibits progressive hypoxia during larval development. Here, we investigate an alternative oxygen-sensing mechanism within this brain compartment, distinct from the canonical hypoxia signaling pathway mediated by HIF. Using genetic tools, immunostaining, and confocal microscopy, we demonstrate that the loss of the atypical soluble guanylyl cyclase (asGC) subunit Gyc88E, or the ectopic expression of Gyc89Db in neural stem cells leads to increased optic lobe volume. We propose the existence of a link between cGMP signaling and neurogenesis in the developing brain.

developmental biology↗

bioRxiv2024

Survival, Movement, and Lifespan: Decoding the Roles of Patched-Related (Ptr) in Drosophila melanogaster

Patched-related (Ptr) is a transmembrane protein implicated in developmental processes in Drosophila melanogaster, yet its precise role remains incompletely understood. Here, we use Ptr23c null mutants to investigate the functional significance of Ptr through the entire life cycle monitoring survival during embryonic, larval, pupal and adult development, and studying larval locomotion and muscle structure. We report that Ptr23c larvae displayed impaired hatching, indicative of defective embryonic development. Moreover, mutant larvae exhibited reduced mobility and lethargy, suggesting a potential involvement of Ptr in neuromuscular function. Morphological analysis of somatic muscles in mutant larvae revealed enlarged cell nuclei. Despite high pre-adult mortality, a subset of Ptr23c mutant adults display an unexpected extension in lifespan compared to controls, implicating Ptr in the regulation of longevity. Our findings provide critical insights into the multifaceted role of Ptr in Drosophila development, highlighting its contributions to post-embryonic survival, neuromuscular function, and lifespan regulation. This study underscores the significance of exploring broader genetic networks to unravel the complexities of developmental processes. Highlights- Loss of Ptr elicits impaired embryonic hatching, reduced mobility, and lethargy. - Ptr23c mutants display nuclear enlargement in somatic muscles. - Ptr23c individuals that survive to adulthood demonstrate extended longevity.

developmental biology↗

bioRxiv2023

Vitamin D deficiency induces erectile dysfunction: role of superoxide

Epidemiological studies suggest a relationship between vitamin D deficiency and erectile dysfunction (ED) but its causal relationship and the mechanism involved are unclear. Here we demonstrate that isolated corpora cavernosa (CC) from human donors with low vitamin D levels show reduced NO-dependent erectile function. This ED is also reproduced in vitamin D deficient rats and vitamin D receptor knockout mice in vivo and ex vivo and is associated with penile fibrosis. Vitamin D deficiency also blunts the response of CC to the phosphodiesterase 5 inhibitor sildenafil. CC from deficient rats show increased superoxide and their impaired erectile function is restored by superoxide scavengers. These results suggest that vitamin D deficiency induces ED via increased superoxide production.

pharmacology and toxicology↗

bioRxiv2019

Compartment and cell type-{-}specific hypoxia responses in the developing Drosophila brain

Environmental factors such as the availability of oxygen are instructive cues to regulate stem cell maintenance and differentiation. We used a genetically encoded biosensor to monitor the hypoxic state of neural cells in the larval brain of Drosophila. The biosensor reveals brain compartment and cell type specific levels of hypoxia. The values correlate with differential tracheolation that is observed throughout development between the central brain and the optic lobe. Neural stem cells in both compartments show the strongest hypoxia response while intermediate progenitors, neurons and glial cells reveal weaker responses. We demonstrate that the distance between a cell and the next closest tracheole is a good predictor of the hypoxic state for that cell. Our model concludes that oxygen availability is the major factor controlling the hypoxia response in the developing Drosophila brain but cell intrinsic and cell-type specific factors contribute to modulate the response in an unexpected manner.

developmental biology↗