Biology subjects

Antinucci, P.

Publications and source records attributed to Antinucci, P..

5 recordsLinked to original sources

bioRxiv2026

Scaling a context-aware genomic model for condition-specific edit design in plants

Engineering agronomically relevant traits in crops often requires changing a gene's activity in a specific tissue, developmental stage or environmental condition while preserving its roles in other contexts. Designing such selective changes requires predicting how cis-regulatory sequences are interpreted in different biological states, as the same edit can have different effects across contexts. Genomic models have made substantial progress in predicting gene expression from DNA sequence, yet sequence-only predictors do not receive an explicit description of biological states. We introduce CROP-1 (Context-aware Regulatory Output Prediction model), which combines DNA sequence with transcription factor binding motifs and measured expression to predict gene activity as a function of both sequence and regulatory state. On a held-out test set spanning six plant species, CROP-1 achieves a median per-gene Pearson correlation across contexts of 0.831, compared with 0.486 for its parameter-matched sequence-only counterpart, and 57-246% higher median correlations than three genomic foundation models fully fine-tuned on the same task. Prediction accuracy also improves with scale: increasing model capacity reduces validation error by 48%, while expanding training data to include more diverse biological contexts reduces it by 58%. We then use gradient-based sequence optimisation to translate a desired gene expression pattern into candidate edits of its cis-regulatory sequence, targeting up- or down-regulation in one context while preserving expression in others. In soybean and tomato, edit designs with 1-20 nucleotide substitutions produce strong predicted target responses and much smaller average changes across non-target contexts. By connecting scalable learning of sequence-state relationships to selective edit design, CROP-1 provides a computational foundation for controlling where, when and under which conditions endogenous crop genes are active.

plant biology↗

bioRxiv2025

Predatory orienting is jointly controlled by optic tectum and pretectum.

The optic tectum and pretectum have been implicated in hunting behaviour in several species but how activity in these regions is coordinated to control target-directed orienting manoeuvres is not understood. We performed two-photon calcium imaging across these brain regions in larval zebrafish, which revealed space and rate-coded premotor activity associated with graded, prey-directed eye and tail movements. Consistent with imaging data, intensity-modulated optogenetic stimulation of pretectum induced progressively more lateralised contraversive orienting behaviour and spatially patterned stimulation of optic tectum revealed a motor map along the anterior-posterior axis that primarily generated ipsiversive responses. Anatomical tracing and laser axotomies indicated that pretectal neurons control contraversive turns via a crossed pretectobulbar pathway whereas optic tectum shows topographically patterned output with a major uncrossed projection to hindbrain. Our data support a model in which premotor activity across pretectum and optic tectum collectively controls predatory orienting via both crossed and uncrossed (pre)-tectobulbar pathways.

neuroscience↗

bioRxiv2020

A simple and effective F0 knockout method for rapid screening of behaviour and other complex phenotypes

Hundreds of human genes are associated with neurological diseases, but translation into tractable biological mechanisms is lagging. Larval zebrafish are an attractive model to investigate genetic contributions to neurological diseases. However, current CRISPR-Cas9 methods are difficult to apply to large genetic screens studying behavioural phenotypes. To facilitate rapid genetic screening, we developed a simple sequencing-free tool to validate gRNAs and a highly effective CRISPR-Cas9 method capable of converting >90% of injected embryos directly into F0 biallelic knockouts. We demonstrate that F0 knockouts reliably recapitulate complex mutant phenotypes, such as altered molecular rhythms of the circadian clock, escape responses to irritants, and multi-parameter day-night locomotor behaviours. The technique is sufficiently robust to knockout multiple genes in the same animal, for example to create the transparent triple knockout crystal fish for imaging. Our F0 knockout method cuts the experimental time from gene to behavioural phenotype in zebrafish from months to one week.

genetics↗

bioRxiv2020

A calibrated optogenetic toolbox of stable zebrafish opsin lines

Optogenetic actuators with diverse spectral tuning, ion selectivity and kinetics are constantly being engineered providing powerful tools for controlling neural activity with subcellular resolution and millisecond precision. Achieving reliable and interpretable in vivo optogenetic manipulations requires reproducible actuator expression and calibration of photocurrents in target neurons. Here, we developed nine transgenic zebrafish lines for stable opsin expression and calibrated their efficacy in vivo. We first used high-throughput behavioural assays to compare opsin ability to elicit or silence neural activity. Next, we performed in vivo whole-cell electrophysiological recordings to quantify the amplitude and kinetics of photocurrents and test opsin ability to precisely control spiking. We observed substantial variation in efficacy, associated with differences in both opsin expression level and photocurrent characteristics, and identified conditions for optimal use of the most efficient opsins. Overall, our calibrated optogenetic toolkit will facilitate the design of controlled optogenetic circuit manipulations.

neuroscience↗

bioRxiv2019

A pretectal command system controls hunting behaviour

For many species, hunting is an innate behaviour that is crucial for survival, yet the circuits that control predatory action sequences are poorly understood. We used larval zebrafish to identify a command system that controls hunting. By combining calcium imaging with a virtual hunting assay, we identified a discrete pretectal region that is selectively active when animals initiate hunting. Targeted genetic labelling allowed us to examine the function and morphology of individual cells and identify two classes of pretectal neuron that project to ipsilateral optic tectum or the contralateral tegmentum. Optogenetic stimulation of single neurons of either class was able to induce sustained hunting sequences, in the absence of prey. Furthermore, laser ablation of these neurons impaired prey-catching and prevented induction of hunting by optogenetic stimulation of the anterior-ventral tectum. In sum, we define a specific population of pretectal neurons that functions as a command system to drive predatory behaviour. Key findingsO_LIPretectal neurons are recruited during hunting initiation C_LIO_LIOptogenetic stimulation of single pretectal neurons can induce predatory behaviour C_LIO_LIAblation of pretectal neurons impairs hunting C_LIO_LIPretectal cells comprise a command system controlling hunting behaviour C_LI

neuroscience↗