Biology subjects

Davis, S. N.

Publications and source records attributed to Davis, S. N..

8 recordsLinked to original sources

bioRxiv2026

Synthetic budding morphogenesis by optogenetic receptor tyrosine kinase signaling

The mammalian kidney relies on a branched network of collecting ducts for fluid transport and homeostasis. Replicating this network in vitro would parallelize function in synthetic replacement kidneys, yet current organoids have limited branching capacity. Here, we establish a developmentally-informed strategy to control organoid budding through optogenetic control of a receptor tyrosine kinase, RET. We first show pharmacological manipulation of RET signaling controls the extent of branching in mouse embryonic kidneys and human stem cell-derived kidney organoids. Next, we develop an optogenetic RET receptor (optoRET) that signals in a ligand-independent manner via blue light-mediated clustering. Epithelial cells expressing optoRET reproduce stereotyped RET signaling, scattering, and symmetry breaking in response to blue light. Human kidney organoids undergo budding with controllable orientation in response to spatially patterned optoRET stimulation. Our results establish ligand-free optogenetic control of branching and inspire new synthetic biology strategies for epithelial organoid design. HighlightsGDNF-RET controls branching and tip cell state in mouse and human kidney tissues. OptoRET reproduces endogenous RET signaling and morphogenesis in cell lines. OptoRET enables ligand-free budding in human renal epithelial organoids. Spatially patterned optoRET stimulation controls budding orientation.

bioengineering↗

bioRxiv2025

Lighting and circadian cues shape locomotor strategies for balance and navigation in larval zebrafish

Most fish are inherently unstable and must swim to stabilize posture. How diurnal fish reduce activity at night while maintaining postural control remains unclear. We defined distinct locomotor strategies that larval zebrafish (Danio rerio) use to control posture and navigate the water column in response to light and circadian cues. In the dark, larvae maintain balance by swimming in long bouts with large nose-up rotations, compensating for nose-down drift accrued during prolonged inactivity. Effective postural compensation requires vestibular sensation from the utricle. By contrast, in the light, larvae navigate with short, frequent, and variable bouts. While lighting exerts a dominant, masking effect on the locomotor strategies, circadian rhythms modulate swim kinematics. Our results reveal distinct light-dark locomotor strategies and disentangle how ambient light and the internal clock jointly shape balance control and navigation. This work lays the foundation for understanding how external and internal cues interact to govern locomotor activity in freely moving diurnal animals.

animal behavior and cognition↗

bioRxiv2024

Birthdate aligns vestibular sensory neurons with central and motor partners across a sensorimotor reflex circuit for gaze stabilization

Developing populations of connected neurons often share spatial and/or temporal features that anticipate their assembly. A unifying spatiotemporal motif might link sensory, central, and motor populations that comprise an entire circuit. In the sensorimotor reflex circuit that stabilizes vertebrate gaze, central and motor partners are paired in time (birthdate) and space (dorso-ventral). To determine if birthdate and/or dorso-ventral organiza-tion could align the entire circuit, we measured the spatial and temporal development of the sensory circuit node: the vestibular ganglion neurons. We discovered that progressive dorsal-to-ventral organization closely predicts vestibular ganglion development, with additional organization along its functional (rostrocaudal) axis. With an acute optical lesion and calcium imaging paradigm, we found that this common spatiotemporal axis anticipated functional sensory-to-central partner matching. We propose a "first-come, first-served" model in which birth-date organizes and assembles the sensory, central, and motor populations that comprise the gaze stabilization circuit, a general strategy for poly-synaptic circuit assembly across embryonically-diverse neural populations. SUMMARY STATEMENTCircuit nodes often develop along common axes. We find that a "first-come, first-served" temporal rule underscores the organization of a canonical sensorimotor circuit for gaze stabilization, simplifying poly-synaptic assembly.

neuroscience↗

bioRxiv2024

Bird Name-a-thon: Categorizing English bird names using crowdsourcing

Common names of species are important for communicating with the general public. In principle, these names should provide an accessible way to engage with and identify species. The common names of species have historically been labile without standard guidelines, even within a language. Currently, there is no systematic assessment of how often common names communicate identifiable and biologically relevant characteristics about species. This is a salient issue in ornithology, where common names are used more often than scientific names for species of birds in written and spoken English, even by professional researchers. To gain a better understanding of the types of terminology used in the English-language common names of bird species, a group of 85 professional ornithologists and non-professional contributors classified unique descriptors in the common names of all recognized species of birds. In the AvianLexiconAtlas database produced by this work, each species common name is assigned to one of ten categories associated with aspects of avian biology, ecology, or human culture. Across 10,906 species of birds, 89% have names describing the biology of the species, while the remaining 11% of species have names derived from human cultural references, human names, or local non-English languages. Species with common names based on features of avian biology are more likely to be related to each other or be from the same geographic region. The crowdsourced data collection also revealed that many common names contain specialized or historic terminology unknown to many of the data collectors, and we include these terms in a glossary and gazetteer alongside the dataset. The AvianLexiconAtlas can be used as a quantitative resource to assess the state of terminology in English-language common names of birds. Future research using the database can shed light on historical approaches to nomenclature and how people engage with species through their names.

zoology↗

bioRxiv2024

Multisensory strategies for postural compensation after lateral line loss

Fish actively control posture in the pitch axis (nose-up/nose-down) to counter instability and regulate their elevation in the water column. To test the hypothesis that environmental cues shape strategies fish use to control posture, we leveraged a serendipitous finding: larval zebrafish (Danio rerio) lose swim bladder volume and sink mildly after acute loss of lateral line hair cells. Using long-term (48 h) recordings of unrestrained swimming, we discovered that sinking larvae compensated differently depending on light conditions. In the dark, they swim more frequently with an increased nose-up posture. In contrast, larvae in the light do not swim more frequently, but do climb more often. Finally, after lateral line regeneration, larvae returned to normal buoyancy and swam comparably to control siblings. We conclude that larvae can switch postural control strategies depending on the availability of visual information. Our findings complement and extend morphological and kinematic analyses of locomotion. More broadly, by quantifying the variation in strategies our work speaks to the evolutionary substrate for different balance behaviors.

neuroscience↗

bioRxiv2023

Nephron progenitors rhythmically alternate between renewal and differentiation in synchrony with kidney branching morphogenesis

The developing mammalian kidney exponentially duplicates nephron-forming stem cell niches at the tips of the urinary collecting duct tree to achieve massively parallel function. Nephron formation rate has a clinically meaningful effect on person-to-person variability in nephron endowment1-5, while exerting in vitro control could enable sustained waves of nephrogenesis in organoid-derived synthetic kidney tissues6,7. However, how the kidney arrives at an appropriate number and ratio of nephrons to collecting ducts is unclear. Here we show that nephron formation is rhythmic and synchronized with branching of the ureteric bud tree (the future urinary collecting ducts). We correlate human and mouse spatial transcriptomics data with the branching life-cycle to uncover rhythmically alternating signatures of nephron progenitor differentiation and renewal. The nephron progenitor rhythm parallels rhythmic nuclear elongation and other hallmarks of mechanical tension in surrounding stromal cells that we attribute to branching-induced deformation. Stroma-specific knockdown of actomyosin activity leads to a striking loss of synchronization between nephron formation and ureteric bud branching without blocking either. These results suggest that the stroma acts as a mechanically entrained pacemaker for nephron formation. Together, our findings uncover a feedback mechanism for clock-like coordination of organ composition during exponential growth.

developmental biology↗

bioRxiv2023

Scalable Apparatus to Measure Posture and Locomotion (SAMPL): a high-throughput solution to study unconstrained vertical behavior in small animals

Balance and movement are impaired in a wide variety of neurological disorders. Recent advances in behavioral monitoring provide unprecedented access to posture and loco-motor kinematics, but without the throughput and scalability necessary to screen candidate genes / potential therapeutics. We present a powerful solution: a Scalable Apparatus to Measure Posture and Locomotion (SAMPL). SAMPL includes extensible imaging hardware and low-cost open-source acquisition software with real-time processing. We first demonstrate that SAMPLs hardware and acquisition software can acquire data from D. melanogaster, C.elegans, and D. rerio as they move vertically. Next, we leverage SAMPLs throughput to rapidly (two weeks) gather a new zebrafish dataset. We use SAMPLs analysis and visualization tools to replicate and extend our current understanding of how zebrafish balance as they navigate through a vertical environment. Next, we discover (1) that key kinematic parameters vary systematically with genetic background, and (2) that such background variation is small relative to the changes that accompany early development. Finally, we simulate SAMPLs ability to resolve differences in posture or vertical navigation as a function of effect size and data gathered - key data for screens. Taken together, our apparatus, data, and analysis provide a powerful solution for laboratories using small animals to investigate balance and locomotor disorders at scale. More broadly, SAMPL is both an adaptable resource for laboratories looking process video-graphic measures of behavior in real-time, and an exemplar of how to scale hardware to enable the throughput necessary for screening.

neuroscience↗

bioRxiv2020

Chloroquine Kills Hair Cells in Zebrafish Lateral Line and Murine Cochlear Cultures: Implications for Ototoxicity

Hearing and balance deficits have been reported during and following treatment with the antimalarial drug chloroquine. However, experimental work examining the direct actions of chloroquine on mechanoreceptive hair cells in common experimental models is lacking. This study examines the effects of chloroquine on hair cells using two common experimental models: the zebrafish lateral line and neonatal mouse cochlear cultures. Zebrafish larvae were exposed to varying concentrations of chloroquine phosphate or hydroxychloroquine for 1 hr or 24 hr, and hair cells assessed by antibody staining. A significant, dose-dependent reduction in the number of surviving hair cells was seen across conditions for both exposure periods. Hydroxycholroquine showed similar toxicity. In mouse cochlear cultures, chloroquine damage was specific to outer hair cells in tissue from the cochlear basal turn, consistent with susceptibility to other ototoxic agents. These findings suggest a need for future studies employing hearing and balance monitoring during exposure to chloroquine and related compounds, particularly with interest in these compounds as therapeutics against viral infections including coronavirus.

neuroscience↗