Biology subjects

Pallares, M. E.

Publications and source records attributed to Pallares, M. E..

3 recordsLinked to original sources

bioRxiv2026

Juvenile behavioral alterations and sex-dependent deficits in hippocampal neurogenesis following early-life stress in rats

Early-life adversity during critical developmental windows markedly increases vulnerability to neuropsychiatric disorders later in life. Although adult behavioral and neurobiological alterations following early stress are well documented, the early emerging phenotypes and their underlying cellular and molecular mechanisms during juvenile development remain poorly understood. In this study, we utilized the translational Scarcity-Adversity Model (SAM) to investigate early behavioral alterations and hippocampal neuroplasticity in juvenile offspring. We characterized the behavioral profile of juvenile subjects exposed to SAM to identify early manifestations of vulnerability. Next, we evaluated hippocampal neurogenesis by quantifying neural progenitor cell proliferation immediately following stress exposure (at postnatal day 13, PND 13) and the short-term survival of newborn neurons (1 week post-labeling) in the dentate gyrus of juvenile offspring. Furthermore, given the functional compartmentalization of the hippocampus, we measured the protein expression of mature BDNF (mBDNF) and its precursor proBDNF across both dorsal and ventral domains. At the behavioral level, SAM-exposed juvenile offspring exhibited increased immobility in the forced swim test alongside impaired spatial memory in the novel object location task. Regarding hippocampal neurogenesis, SAM exposure did not alter immediate progenitor proliferation at PND 13; however, it produced a significant, male-specific reduction in newborn neuron survival, concomitant with a trend toward decreased mBDNF levels in males. Together, these results provide critical insight into the early neurodevelopmental trajectories triggered by early-life adversity, identifying early behavioral impairments and male-specific neuroplastic deficits as key juvenile markers of vulnerability preceding adult psychopathology.

animal behavior and cognition↗

bioRxiv2022

Stiffness-dependent active wetting enables optimal collective cell durotaxis

The directed migration of cellular clusters enables morphogenesis, wound healing, and collective cancer invasion. Gradients of substrate stiffness are known to direct the migration of cellular clusters in a process called collective durotaxis, but underlying mechanisms remain unclear. Here, we unveil a connection between collective durotaxis and the wetting properties of cellular clusters. We show that clusters of cancer cells dewet soft substrates and wet stiff ones. At intermediate stiffness, at the crossover from low to high wettability, clusters on uniform-stiffness substrates become maximally motile, and clusters on stiffness gradients exhibit optimal durotaxis. Durotactic velocity increases with cluster size, stiffness gradient, and actomyosin activity. We demonstrate this behavior on substrates coated with the cell-cell adhesion protein E-cadherin and then establish its generality on substrates coated with extracellular matrix. We develop a physical model of three-dimensional active wetting that explains this mode of collective durotaxis in terms of a balance between in-plane active traction and tissue contractility, and out-of-plane surface tension. Finally, we show that the distribution of cluster displacements has a heavy tail, with infrequent but large cellular hops that contribute to durotactic migration. Our study demonstrates a physical mechanism of collective durotaxis, through both cell-cell and cell-substrate adhesion ligands, based on the wetting properties of active droplets.

biophysics↗

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↗