Biology subjects

David, D.

Publications and source records attributed to David, D..

4 recordsLinked to original sources

bioRxiv2025

APETALA2 controls seed growth by regulating outer integument mechanical identity during seed coat differentiation

Organ morphogenesis requires differentiating cells to acquire mechanical properties that precisely regulate growth. In Arabidopsis thaliana, seed size and shape are largely controlled by the outer integument of the seed coat, whose two layers develop distinct mechanical behaviors critical for growth regulation. Here, we show that the cell identity factor APETALA2 (AP2) both promotes and restricts seed growth by coordinating the post-fertilization differentiation of these layers into distinct seed coat tissues. AP2 drives layer-specific remodeling of cell wall composition, notably affecting pectin and xyloglucan, thereby establishing contrasting mechanical properties between the two layers. Unexpectedly, these changes in wall composition and mechanics do not alter mechanosensitive responses, revealing a surprising uncoupling between cell wall remodeling and mechanotransduction. Our findings identify AP2 as a key coordinator of tissue-specific mechanical differentiation during organ morphogenesis.

plant biology↗

bioRxiv2025

Identification of a Thermogenic Target in the Dorsal Raphe Nucleus for Weight Management

Obesity emerges from a complex interplay of factors, including imbalanced interoception, genetic predisposition, and environmental cues, ultimately disrupting body weight homeostasis1. While much research has concentrated on strategies to suppress appetite for sustained weight loss, insufficient attention has been given to counterregulatory mechanisms that promote energy expenditure. Here, we show that chronic inhibition of GABAergic neurons in the Dorsal Raphe Nucleus (DRNVGAT) reduces body weight in diet-induced obese (DIO) mice. In this study, molecular profiling and in-situ hybridization in rodent and human brains revealed that the constitutively activated orphan receptor GPR6 is selectively enriched in DRNVGAT neurons. We next developed and administered a potent and highly selective GPR6 inverse agonist, which significantly reduced weight gain in DIO mice by stimulating brown adipose tissue thermogenesis without affecting appetite. Altogether, this study transitions from transcriptomic profiling, high-throughput drug screening and metabolic phenotyping to successfully identify a novel candidate to treat obesity.

neuroscience↗

bioRxiv2025

COVID-19 vaccination induces cross-neutralisation of sarbecoviruses related to SARS-CoV-2

Close relatives of SARS-CoV-1 and SARS-CoV-2 continue to circulate in wildlife, posing an ongoing threat of zoonotic spillover. While vaccination played a key role in controlling the COVID-19 pandemic, variants of concern (VOC) with immune evasive substitutions emerged on multiple occasions, causing widespread breakthrough infections. The combined threats of zoonosis and newly emerging VOCs, coupled with the potential for recombination, underscore the need to assess the breadth of existing vaccine-mediated protection. Here, we investigate a cohort of older individuals (median age 68.5 years) for the potential of cross-neutralisation against Omicron lineage VOC and animal sarbecoviruses induced by four COVID-19 vaccine doses. Despite the recent use of a bivalent mRNA vaccine dose (encoding spike from Wu-1 and omicron), we observed that neutralisation of Omicron lineage VOCs such as BA.1 and BA.2 were reduced compared to SARS-CoV-2 Wu-1, suggesting an imprinted immune response from pre-Omicron lineage viruses. Similarly, both SARS-CoV-1 and a SARS-CoV-1-related bat CoV were neutralised less efficiently than SARS-CoV-2 Wu-1. Unexpectedly, however, we observed that two animal SARS-CoV-2-related viruses, BANAL-20-52 (from bats) and a pangolin-CoV, were more sensitive to serum neutralising antibodies than SARS-CoV-2 Wu-1 itself. These surprising findings suggest that vaccine-mediated adaptive immunity may provide efficient cross-protection against certain animal sarbecoviruses.

microbiology↗

bioRxiv2025

Neural correlates in basolateral and central amygdala during reward seeking in the face of punishment

The inability to suppress actions despite adverse consequences is a hallmark of compulsive behaviors and is amygdala dependent. To study the amygdalas role in responding despite adverse consequences, we compared single-unit activity in the basolateral (BLA) or central (CeA) amygdala before and after reward-seeking under punishment threat. Rats started each trial by pressing an initial lever, which triggered an outcome-specific 5-s auditory cue (white noise, pure tone, or clicker), signaling one of three reinforcement conditions: 100% sucrose reward, 20% reward/80% omission, or 80% reward/20% footshock punishment. Next, the active and inactive levers were extended, and pressing on the active lever terminated the auditory cue and triggered an outcome-specific 1-s visual cue predicting either reward, reward omission, or shock. After training, we implanted eight tetrodes in the BLA (n=7) or CeA (n=5) and recorded single-unit activity of [~]100 neurons per region during task performance. CeA neurons, and to a lesser extent BLA neurons, responded differently to the distinct auditory cues and outcomes. The discrimination between conditions partially explained the capacity of neuronal activity to predict the latency to lever press to complete the trial. The failure to suppress reward-seeking behavior in the face of punishment coincided with the reactivation of reward-seeking-sensitive and the loss of inhibition of punishment-sensitive neuronal populations. In conclusion, we found that after extended training, opposing populations of activated and inhibited neurons in CeA, and to a lesser extent in BLA, control completion of reward-seeking despite punishment.

neuroscience↗