Biology subjects

Fotowat, H.

Publications and source records attributed to Fotowat, H..

5 recordsLinked to original sources

bioRxiv2025

Self-Organizing Neural Networks in Novel Moving Bodies: Anatomical, Behavioral, and Transcriptional Characterization of a Living Construct with a Nervous System

A great deal is known about the formation and architecture of biological neural networks in animal models, which have arrived at their current structure-function relationship through evolution by natural selection. Little is known about the development of such structure-function relationships in a scenario where neurons are allowed to grow within evolutionarily-novel, motile bodies. Previous work showed that when a piece of ectodermal tissue is excised from Xenopus embryos and allowed to develop ex vivo, it will develop into a three-dimensional (3D) mucociliary organoid, and exhibits behaviors different from those observed in tadpoles of the same age. These biological robots or biobots are autonomous, self-powered, and able to move through aqueous environments. Here we report a novel type of biobot that is composed of ciliated epidermis and additionally incorporates neural tissue (neurobots). We show that neural precursor cells implanted within the Xenopus skin constructs develop into mature neurons and extend processes towards the outer surface of the bot as well as among each other. These self-organized neurobots show distinct external morphology, generate more complex patterns of spontaneous movements, and are differentially affected by neuroactive drugs compared to their non-neuronal counterparts. Calcium imaging experiments show that neurons within neurobots are indeed active. Transcriptomics analysis of the neurobots reveals increased variability of transcript profiles, expression of a plethora of genes relating to nervous system development and function, a shift toward more ancient genes, and up-regulation of neuronal genes implicated in visual perception.

bioengineering↗

bioRxiv2023

Identification of a pharmaceutical biostasis inducer that slows metabolism in multiple vertebrates that do not hibernate

Drugs that induce reversible slowing of metabolic and physiological processes would have great value for organ preservation, especially for organs with high susceptibility to hypoxia-reperfusion injury, such as the heart. Using whole-organism screening of metabolism, mobility, and development in Xenopus, we identified an existing drug, SNC80, that rapidly and reversibly slows biochemical and metabolic activities while preserving cell and tissue viability. Although SNC80 was developed as a delta opioid receptor activator, we discovered that its ability to slow metabolism is independent of its opioid modulating activity as a novel SNC80 analog (WB3) with almost 1,000 times less delta opioid receptor binding activity is equally active. Metabolic suppression was also achieved using SNC80 in microfluidic human organs-on-chips, as well as in explanted whole porcine hearts and limbs, demonstrating the cross-species relevance of this approach and potential clinical relevance for surgical transplantation. Pharmacological induction of physiological slowing in combination with organ perfusion transport systems may offer a new therapeutic approach for tissue and organ preservation for transplantation, trauma management, and enhancing patient survival in remote and low-resource locations.

bioengineering↗

bioRxiv2023

Transplantation-based screen uncovers inducers of muscle progenitor cell engraftment across vertebrate species

Stem cell transplantation presents a potentially curative strategy for genetic disorders of skeletal muscle, but this approach is limited due to the deleterious effects of cell expansion in vitro and consequent poor engraftment efficiency. In an effort to overcome this limitation, we sought to identify molecular signals that enhance the myogenic activity of cultured muscle progenitors. Here, we report the development and application of a cross-species small molecule screening platform employing zebrafish and mouse, which enables rapid, direct evaluation of the effects of chemical compounds on the engraftment of transplanted muscle precursor cells. Using this system, we screened a library of bioactive lipids to identify those that could increase myogenic engraftment in vivo in zebrafish and mice. Two lipids, lysophosphatidic acid (LPA) and niflumic acid (NFA), are linked to activation of intracellular calcium ion flux, which showed conserved, dose-dependent and synergistic effects in promoting muscle engraftment across these vertebrate species.

cell biology↗

bioRxiv2022

Neural circuits underlying habituation of visually evoked escape behaviors in larval zebrafish

Larval zebrafish that are exposed repeatedly to dark looming stimuli will quickly habituate to these aversive signals and cease to respond with their stereotypical escape swims. A dark looming stimulus can be separated into two independent components: one that is characterized by an overall spatial expansion, where overall luminance is maintained at the same level, and a second, that represents an overall dimming within the whole visual field in the absence of any motion energy. Using specific stimulation patterns that isolate these independent components, we first extracted the behavioral algorithms that dictate how these separate information channels interact with each other and across the two eyes during the habituation process. Concurrent brain wide imaging experiments then permitted the construction of circuit models that suggest the existence of three separate neural pathways. The first is a looming channel which responds specifically to concentrically expanding edges and relays that information to the brain stem escape network to generate directed escapes. The second is a dimming specific channel that serves to support and amplify the looming pathway. While the looming channel operates in a purely monocular fashion where stimuli are relayed exclusively to the contralateral hemisphere, dimming responses are processed in both monocular and binocular pathways. Finally, we identify a third, separate and largely monocular, dimming channel that appears to specifically inhibit escape responses when activated. We propose that, unlike the first two channels, this third channel is under strong contextual modulation and that it is primarily responsible for the incremental silencing of successive dark looming evoked escapes.

neuroscience↗

bioRxiv2018

Neural activity in a hippocampus-like region of the teleost pallium are associated with navigation and active sensing

Neural mechanisms underlying spatial navigation in fish are unknown and little is known, for any vertebrate, about the relationship between active sensing and the formation of spatial maps. The weakly electric fish, Gymnotus Carapo, uses their active electric sense for spatial navigation. The electric organ discharge rate (EODr) undergoes transient increases during navigation to enhance electrosensory sampling. Gymnotus also uses stereotyped forward/ backward swimming as a second form of active sensing that brings objects towards the electroreceptor-dense head region. We wirelessly recorded neural activity from the pallium of freely swimming Gymnotus. Spiking activity was sparse and occurred only during swimming. Notably, some units exhibited significant place specificity and/or association with both forms of active sensing. Our results provide the first characterization of neural activity in a hippocampal-like region of a teleost fish brain and connects active sensing via sensory sampling rate and directed movements to higher order encoding of spatial information.

neuroscience↗