Biology subjects

Gelnaw, H.

Publications and source records attributed to Gelnaw, H..

5 recordsLinked to original sources

bioRxiv2026

Transcriptional profiling of extraocular motor neurons reveals sim1a as a candidate strabismus-related gene

Strabismus, or misalignment of the eyes, is a heritable disorder frequently associated with vision loss and decreased quality of life. Incomitant strabismus, where the degree of misalignment differs based on gaze angle, can arise from mutations in genes that regulate the development of extraocular motor neurons. To date, few such genes have been identified. The extraocular motor system is highly conserved across vertebrates, suggesting a comparative transcriptomic discovery approach would be fruitful. Using bulk and single-cell sequencing in a small accessible vertebrate, the larval zebrafish, we identified genes expressed in subpopulations of extraocular motor neurons in cranial nuclei nIII/nIV. We next assessed extraocular motor neuron number and vestibulo-ocular reflex performance after CRISPR/Cas9-mediated mutagenesis of three genes with suggestive expression patterns: sim1a, nav2a, one-cut1, and one known to disrupt nIII/nIV motor neuron specification: phox2a. Loss of sim1a impaired the vestibulo-ocular reflex without change to nIII/nIV motor neuron number. Our data suggest that constitutive disruptions to sim1a can impair nIII/nIV-dependent eye movements. More broadly, our work illuminates considerable transcriptomic diversity among extraocular motor neuron subpopulations, and establishes a pipeline to identify genes relevant to ocular motor disease etiology.

neuroscience↗

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

Tau load in select brainstem neurons predicts the severity and nature of balance deficits in the absence of cell death

Patients with tauopathies present with profoundly different clinical symptoms1, even within the same disorder2. A central hypothesis in the field, well-supported by biomarker studies3,4 and post-mortem pathology5-7, is that clinical heterogeneity reflects differential degeneration of vulnerable neuronal populations responsible for specific neurological functions. Recent work has revealed mechanisms underlying susceptibility of particular cell types8-10, but relating tau load to disrupted behavior -- es- pecially before cell death -- requires a targeted circuit-level approach. Here we studied two distinct balance behaviors in larval zebrafish11 expressing a human 0N/4R-tau allele12 in select populations of evolutionarily-conserved and well-characterized brainstem vestibular circuits13,14. We observed that human tau load predicted the severity of circuit-specific deficits in posture and navigation in the ab- sence of cell death. Targeting expression to either mid- or hindbrain balance neurons recapitulated these particular deficits in posture and navigation. By parametrically linking tau load in specific neu- rons to early behavioral deficits, our work moves beyond cell type to close the gap between pathological and neurological conceptions of tauopathy.

neuroscience↗

bioRxiv2024

A brainstem circuit for gravity-guided vertical navigation

The sensation of gravity anchors our perception of the environment and is crucial for navigation. However, the neural circuits that transform gravity into commands for navigation are undefined. We first determined that larval zebrafish (Danio rerio) navigate vertically by maintaining a consistent heading across a series of upward climb or downward dive bouts. Gravity-blind mutant fish swim with more variable heading and excessive veering, leading to inefficient vertical navigation. After targeted photoablation of ascending vestibular neurons and spinal projecting midbrain neurons, but not vestibulospinal neurons, vertical navigation was impaired. These data define a sensorimotor circuit that uses evolutionarily-conserved brainstem architecture to transform gravitational signals into persistent heading for vertical navigation. The work lays a foundation to understand how vestibular inputs allow animals to move efficiently through their environment.

neuroscience↗

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↗