Biology subjects

Issa, A. R.

Publications and source records attributed to Issa, A. R..

3 recordsLinked to original sources

bioRxiv2021

A novel post-developmental role of the Hox genes underlies normal adult behaviour

The molecular mechanisms underlying the stability of mature neurons and neural circuits are poorly understood. Here we explore this problem and discover that the Hox genes are a component of the genetic programme that maintains normal neural function in adult Drosophila. We show that post-developmental downregulation of the Hox gene Ultrabithorax (Ubx) in adult neurons leads to substantial anomalies in flight. Mapping the cellular basis of these effects reveals that Ubx is required within a subset of dopaminergic neurons, and cell circuitry analyses and optogenetics allow us to link these dopaminergic neurons to flight control. Functional imaging experiments show that Ubx is necessary for normal dopaminergic activity, and neuron-specific RNA-sequencing defines two previously uncharacterised ion channel-encoding genes as potential mediators of Ubx behavioural roles. Our study thus reveals a novel role of the Hox system in controlling adult behaviour and neural function.

neuroscience↗

bioRxiv2020

A physical theory of larval Drosophila behaviour

All animal behaviour must ultimately be governed by physical laws. As a basis for understanding the physics of behaviour in a simple system, we here develop an effective theory for the motion of the larval form of the fruitfly Drosophila melanogaster, and compare it against a quantitative analysis of the real animals behaviour. We first define a set of fields which quantify stretching, bending, and twisting along the larvas antero- posterior axis, and then perform a search in the space of possible theories that could govern the long-wavelength physics of these fields, using a simplified approach inspired by the renormalisation group. Guided by symmetry considerations and stability requirements, we arrive at a unique, analytically tractable free-field theory with a minimum of free parameters. Unexpectedly, we are able to explain a wide-spectrum of features of Drosophila larval behaviour by applying equilibrium statistical mechanics: our theory closely predicts the animals postural modes (eigenmaggots), as well as distributions and trajectories in the postural mode space across several behaviours, including peristaltic crawling, rolling, self-righting and unbiased substrate exploration. We explain the low-dimensionality of postural dynamics via Boltzmann suppression of high frequency modes, and also propose and experimentally test, novel predictions on the relationships between different forms of body deformation and animal behaviour. We show that crawling and rolling are dominated by similar symmetry properties, leading to identical dynamics/statistics in mode space, while rolling and unbiased exploration have a common dominant timescale. Furthermore, we are able to demonstrate that self-righting behaviour occurs continuously throughout substrate exploration, owing to the decoupling of stretching, bending, and twisting at low energies. Together, our results demonstrate that relatively simple effective physics can be used to explain and predict a wide range of animal behaviours.

biophysics↗

bioRxiv2020

microRNA-dependent control of sensory neuron function regulates posture behaviour in Drosophila

All what we see, touch, hear, taste or smell must first be detected by the sensory elements in our nervous system. Sensory neurons, therefore, represent a critical component in all neural circuits and their correct function is essential for the generation of behaviour and adaptation to the environment. Here we report that a gene encoding the evolutionarily conserved microRNA (miRNA) miR-263b, plays a key behavioural role in Drosophila through effects on the function of larval sensory neurons. Several independent experiments support this finding. First, miRNA expression analysis by means of a miR-263b reporter line, and fluorescent-activated cell sorting coupled to quantitative PCR, both demonstrate expression of miR-263b in Drosophila larval sensory neurons. Second, behavioural tests in miR-263b null mutants show defects in self-righting: an innate and evolutionarily conserved posture control behaviour that allows the larva to return to its normal position if turned upside-down. Third, competitive inhibition of miR-263b in sensory neurons using a miR-263b sponge leads to self-righting defects. Fourth, systematic analysis of sensory neurons in miR-263b mutants shows no detectable morphological defects in their stereotypic pattern. Fifth, genetically-encoded calcium sensors expressed in the sensory domain reveal a reduction in neural activity in miR-263b null mutants. Sixth, miR-263b null mutants show a reduced touch-response behaviour and a compromised response to sound, both characteristic of larval sensory deficits. Furthermore, bioinformatic miRNA target analysis, gene expression assays, and behavioural phenocopy experiments suggest that miR-263b might exert its effects - at least in part - through repression of the bHLH transcription factor atonal. Altogether, our study suggests a model in which miRNA-dependent control of transcription factor expression affects sensory function and behaviour. Building on the evolutionary conservation of miR-263b, we propose that similar processes may modulate sensory function in other animals, including mammals.

neuroscience↗