Biology subjects

Wee, C. L.

Publications and source records attributed to Wee, C. L..

6 recordsLinked to original sources

bioRxiv2025

Comparative transcriptomics of lateral hypothalamic cell types reveals conserved growth hormone-tachykinin dynamics in feeding

The lateral hypothalamus (LH) is a highly heterogeneous brain region regulating hunger and motivated behaviors. In zebrafish, the LH shows distinct neural activity across hunger, feeding, and satiety states. However, the functional and evolutionary conservation of relevant neural circuits remain unclear. Using integrative transcriptomics of zebrafish and mouse LH, we identify conserved cellular clusters with shared molecular markers, particularly within GABAergic neurons. We highlight a conserved GABAergic population expressing tachykinin and growth hormone receptors, which is responsive to food cues and modulated by hunger and feeding states. This cluster may mediate acute appetite-enhancing effects of growth hormone. In both species, feeding elevates growth hormone receptor and tachykinin expression and activates these neurons, while human growth hormone increases their activity and food intake in zebrafish. These findings suggest a conserved neural mechanism by which metabolic hormones influence feeding behavior. Our comparative LH atlas highlights the evolutionary biology of appetite regulation and the integration of hormonal and neural signals driving energy homeostasis.

neuroscience↗

bioRxiv2023

Dynamics of endogenous and water cortisol release in Asian Seabass Lates calcarifer after acute stress in a farm scale recirculating aquaculture system

Stress in farmed fish is associated with poor feeding, slow growth, disease, and mortality. Therefore, it is essential to closely monitor the stress levels in fish to optimize farming practices which could then enhance productivity and welfare in aquaculture operations. Cortisol, a stress hormone that can be found in the blood, is a reliable biomarker for evaluating fish stress. As blood sampling is highly invasive, alternative cortisol sampling methods such as fin, mucus, and the surrounding water which contains released cortisol, have been proposed as less invasive or non-invasive sampling methods. However, a comprehensive understanding of their temporal dynamics and associations with plasma cortisol levels is still lacking. In this study, we subjected Lates calcarifer, Asian sea bass within a farm-scale (3,000 L tank, 9,000 L system) high-flow rate (8,000 L/hour) Recirculating Aquaculture System (RAS) to an acute handling stress challenge specifically involving chasing and air exposure, and quantified cortisol dynamics both within different biological samples including blood, fin, and mucus and in tank water from multiple sampling points. We showed that handling stress induced an expected increase in plasma and mucosal cortisol, peaking at 1 hour and 24-48 hours, respectively, and that plasma and mucus cortisol were moderately correlated, especially during the stress period. Fin cortisol did not show consistent dynamics. Water cortisol similarly rose, but peaked within 40 minutes from the start of the stressor, in a pattern that was dependent on the site of sampling within the RAS system, likely due to RAS circulation dynamics. Our study is the first to examine the impact of stress on cortisol accumulation and release in Asian Sea bass in a farm-scale RAS, thus complementing existing research on the efficacy of fin, mucus, and water cortisol as stress indicators that could help optimize aquaculture productivity and welfare.

physiology↗

bioRxiv2020

Social isolation modulates appetite and defensive behavior via a common oxytocinergic circuit in larval zebrafish

Animal brains have evolved to encode social stimuli and transform these representations into advantageous behavioral responses. The commonalities and differences of these representations across species are not well-understood. Here, we show that social isolation activates an oxytocinergic (OXT), nociceptive circuit in the larval zebrafish hypothalamus and that chemical cues released from conspecific animals are potent modulators of this circuits activity. We delineate an olfactory to subpallial pathway that transmits chemical social cues to OXT circuitry, where they are transformed into diverse outputs simultaneously regulating defensive and feeding behaviors. Our data allow us to propose a model through which social stimuli are integrated within a fundamental neural circuit to mediate diverse adaptive behaviours.

neuroscience↗

bioRxiv2020

BRAWNIN: A sORF-encoded Peptide Essential for Vertebrate Mitochondrial Complex III Assembly

The emergence of small open reading frame (sORF)-encoded peptides (SEPs) is rapidly expanding the known proteome at the lower end of the size distribution1,2. Here, we show that the mitochondria proteome is enriched for proteins smaller than 100 a.a. (defined as SEPs). Using a mitochondrial prediction and validation pipeline for small open-reading-frame (sORF)-encoded peptides (SEPs), we report the discovery of 16 endogenous mitochondrial SEPs (mito-SEPs) associated with oxidative phosphorylation (OXPHOS). Through functional prediction, proteomics, metabolomics and metabolic flux modeling, we demonstrate that BRAWNIN (BR), a 71 amino acid peptide encoded by the C12orf73 gene, is essential for respiratory chain complex III (CIII) assembly. In human cells, BR is induced by the energy-sensing AMPK pathway, and its depletion impairs mitochondrial ATP production. In vivo, BR is enriched in muscle tissues and its maternal zygotic deletion in zebrafish causes complete CIII loss, resulting in severe growth retardation, lactic acidosis and early death. Our findings demonstrate that BR is essential for oxidative phosphorylation across vertebrate species. We propose that mito-SEPs are an untapped resource for essential regulators of oxidative metabolism.

cell biology↗

bioRxiv2019

Probabilistic Models of Larval Zebrafish Behavior: Structure on Many Scales

Nervous systems have evolved to combine environmental information with internal state to select and generate adaptive behavioral sequences. To better understand these computations and their implementation in neural circuits, natural behavior must be carefully measured and quantified. Here, we collect high spatial resolution video of single zebrafish larvae swimming in a naturalistic environment and develop models of their action selection across exploration and hunting. Zebrafish larvae swim in punctuated bouts separated by longer periods of rest called interbout intervals. We take advantage of this structure by categorizing bouts into discrete types and representing their behavior as labeled sequences of bout-types emitted over time. We then construct probabilistic models - specifically, marked renewal processes - to evaluate how bout-types and interbout intervals are selected by the fish as a function of its internal hunger state, behavioral history, and the locations and properties of nearby prey. Finally, we evaluate the models by their predictive likelihood and their ability to generate realistic trajectories of virtual fish swimming through simulated environments. Our simulations capture multiple timescales of structure in larval zebrafish behavior and expose many ways in which hunger state influences their action selection to promote food seeking during hunger and safety during satiety.

animal behavior and cognition↗

bioRxiv2019

A bidirectional network for appetite control in zebrafish

Medial and lateral hypothalamic loci are known to suppress and enhance appetite, respectively, but the dynamics and functional significance of their interaction have yet to be explored. Here we report that, in larval zebrafish, primarily serotonergic neurons of the ventromedial caudal hypothalamus (cH) become increasingly active during food deprivation, whereas activity in the lateral hypothalamus (LH) is reduced. Exposure to food sensory and consummatory cues reverses the activity patterns of these two nuclei, consistent with their representation of opposing internal hunger states. Baseline activity is restored as food-deprived animals return to satiety via voracious feeding. The antagonistic relationship and functional importance of cH and LH activity patterns were confirmed by targeted stimulation and ablation of cH neurons. Collectively, the data allow us to propose a model in which these hypothalamic nuclei regulate different phases of hunger and satiety and coordinate energy balance via antagonistic control of distinct behavioral outputs.

neuroscience↗