Biology subjects

Zoeller, D.

Publications and source records attributed to Zoeller, D..

6 recordsLinked to original sources

bioRxiv2026

Spinal injury induces a stem cell-like progenitor state that promotes regenerative neurogenesis via clcf1 in zebrafish.

After spinal injury, zebrafish, in contrast to mammals, show regenerative neurogenesis, characterized by enhanced injury-induced proliferation of ependymo-radial glial cells (ERGs) and an increase in injury-induced generation of neurons from these progenitors. It is unclear whether regenerative neurogenesis simply recapitulates development or uses regeneration-specific mechanisms. Using scRNA-seq and in vivo validation we find a spinal injury-induced state in ERGs (iiERGs) in larval zebrafish. This cell state emerges mostly without proliferation and has stem cell characteristics, including weak expression of neurogenic genes and strong expression of stemness factors, such as lin28a. Expression of lin28a is not detectable during ongoing developmental neurogenesis. Following spinal cord lesion, lin28a disruption increases the numbers of ERGs undergoing neuronal differentiation and of newly-generated neurons, at the expense of proliferating ERGs and iiERGs. This supports a stemness-preserving role of lin28a in iiERGs. Importantly, iiERGs secrete growth factors, including the regeneration-specific cytokine clcf1, which depends in part on lin28a expression. Disruption of clcf1 signalling impairs spinal progenitor proliferation and injury-induced generation of new neurons, but does not affect the emergence of iiERGs. Over-expression of clcf1 is sufficient to augment neurogenesis in unlesioned animals without inducing the iiERG state, indicating that clcf1 acts as a generic growth factor. Hence, we describe an injury-specific stem cell-like ERG population that regulates regenerative neurogenesis by attenuating neuronal differentiation via lin28a and promoting progenitor proliferation via clcf1.

neuroscience↗

bioRxiv2026

Tachykinin neuropeptides are involved in axonal and synaptic differentiation of the pioneer motor axon in zebrafish

In contrast to many other developing systems, in which axon pathfinding and synaptogenesis are separated in time, the pioneering axon of the individually identifiable caudal primary motor neuron in embryonic zebrafish forms en passant synapses during its stereotypical ventral growth. How simultaneous synaptic differentiation and axon pathfinding are coordinated is not fully understood. Here we ask what the role of the tac1 gene, coding for the synaptic tachykinin neuropeptides, is in this unique axon differentiation process. The gene is expressed during axon outgrowth and its disruption results in increased branch length of CaP axons and subtle morphological defects of the pre-synapse. These abnormalities are accompanied by a robust [~]1.5-fold increase in motor neuron activity and in spontaneous early contractions in tac1-deficient embryos. Furthermore, pharmacological inhibition of the tachykinin receptor (Tacr1) leads to altered CaP axonal morphology, mimicking the axonal phenotype observed in tac1-deficient zebrafish. These findings suggest that tachykinin neuropeptides modulate formation and activity of en passant synapses and prevent aberrant axon branching during growth of zebrafish motor axons. HIGHLIGHTS- tac1 refines CaP primary motor axon development in zebrafish - Loss of tac1 disrupts presynaptic maturation at the horizontal myoseptum - tac1 mutants show elevated motor neuron activity and spontaneous contractions

neuroscience↗

bioRxiv2024

Macrophage crosstalk with neural progenitors and fibroblasts controls regenerative neurogenesis via Sema4ab after spinal cord injury in zebrafish

Zebrafish, in contrast to mammals, regenerate neurons after spinal cord injury, but little is known about the control mechanisms of this process. Here we use scRNA-seq and in vivo experiments to show that sema4ab, mainly expressed by lesion-reactive microglia, attenuates regenerative neurogenesis by changing the complex lesion environment. After spinal injury, disruption of sema4ab doubles the number of newly generated progenitor cells and neurons but attenuates axon regrowth and recovery of swimming function. Disruption of the plxnb1a/b receptors, selectively expressed by neural progenitor cells, increases regenerative neurogenesis. In addition, disruption of sema4ab alters activation state and cytokine expression of microglia, such that fibroblasts increase expression of the cytokine tgfb3, which strongly promotes regenerative neurogenesis. Hence, sema4ab in microglia attenuates regenerative neurogenesis in multiple ways, likely directly through plxnb1a/b receptors and indirectly, by controlling the inflammatory milieu and tgfb3 levels. Targeting Sema4A-dependent signalling in non-regenerating vertebrates may be a future strategy to improve regenerative outcomes. HIGHLIGHTS- Microglia suppress pro-regenerative fibroblast signalling in a spinal injury site - Fibroblasts promote regenerative neurogenesis via Tgfb3 signalling - sema4ab promotes microglia activation state after spinal injury - scRNA-seq reveals full complement of sema4ab-dependent changes on different cell types during repair of a spinal lesion site

neuroscience↗

bioRxiv2020

Unraveling the Developmental Dynamic of Visual Exploration of Social Interactions in Autism

Atypical deployment of social gaze is present early on in toddlers with autism spectrum disorders (ASDs). Yet, studies characterizing the developmental dynamic behind it are scarce. Here we used a data-driven method to delineate the developmental change in visual exploration of social interaction over childhood years in autism. Longitudinal eye-tracking data were acquired as children with ASD and their typically developing (TD) peers freely explored a short cartoon movie. We found divergent moment-to-moment gaze patterns in children with ASD compared to their TD peers. This divergence was particularly evident in sequences that displayed social interactions between characters and even more so in children with lower developmental and functional levels. The basic visual properties of the animated scene did not account for the enhanced divergence. Over childhood years, these differences dramatically increased to become more idiosyncratic. These findings suggest that social attention should be targeted early in clinical treatments.

neuroscience↗

bioRxiv2019

Structural control energy of resting-state functional brain states reveals inefficient brain dynamics in psychosis vulnerability.

How the brains white-matter anatomy constrains brain activity is an open question that might give insights into the mechanisms that underlie mental disorders such as schizophrenia. Chromosome 22q11.2 deletion syndrome (22q11DS) is a neurodevelopmental disorder with an extremely high risk for psychosis providing a test case to study developmental aspects of schizophrenia. In this study, we used principles from network control theory to probe the implications of aberrant structural connectivity for the brains functional dynamics in 22q11DS. We retrieved brain states from resting-state functional magnetic resonance images of 78 patients with 22q11DS and 85 healthy controls. Then, we compared them in terms of persistence control energy; i.e., the control energy that would be required to persist in each of these states based on individual structural connectivity and a dynamic model. Persistence control energy was altered in a broad pattern of brain states including both energetically more demanding and less demanding brain states in 22q11DS. Further, we found a negative relationship between persistence control energy and resting-state activation time, which suggests that the brain reduces energy by spending less time in energetically demanding brain states. In patients with 22q11DS, this behavior was less pronounced, suggesting a dynamic inefficiency of brain function in the disease. In summary, our results provide initial insights into the dynamic implications of altered structural connectivity in 22q11DS, which might improve our understanding of the mechanisms underlying the disease.

neuroscience↗

bioRxiv2019

Large-scale brain network dynamics provide a measure of psychosis and anxiety in 22q11.2 deletion syndrome.

Prodromal positive psychotic symptoms and anxiety are two strong risk factors for schizophrenia in 22q11.2 deletion syndrome (22q11DS). The analysis of large-scale brain network dynamics during rest is promising to investigate aberrant brain function and identify potentially more reliable biomarkers. We retrieved and examined dynamics of large-scale functional brain networks using innovation-driven co-activation patterns (iCAPs) and probed into functional signatures of prodromal psychotic symptoms and anxiety. Patients with 22q11DS had shorter activation in cognitive brain networks and longer activation in emotion processing networks. Functional signatures of prodromal psychotic symptoms confirmed an implication of cingulo-prefrontal salience network activation duration and coupling. Functional signatures of anxiety un-covered an implication of amygdala activation and coupling, indicating differential roles of dorsal and ventral sub-divisions of anterior cingulate and medial prefrontal cortices. These results confirm that the dynamic nature of brain network activation contains essential function to develop clinically relevant imaging markers of psychosis vulnerability.

neuroscience↗