Biology subjects

Blanton, C.

Publications and source records attributed to Blanton, C..

3 recordsLinked to original sources

bioRxiv2026

Tenascin N contributes to spinal motor nerve morphogenesis during development

Spinal motor nerves are an integral component of the nervous system whose development requires the coordination of many diverse cell types, including motor neurons, glia, and muscle. Although several molecular mechanisms guiding these interactions are known, many remain to be uncovered. Extracellular matrix (ECM) proteins also play a critical role in motor nerve assembly, yet their functions are less understood compared to classical pathfinding and guidance cues. Here, we identify a role for tenascin-n (tnn), an ECM glycoprotein, in spinal motor nerve development in zebrafish. Using in situ hybridization and immunohistochemistry, we show that tnn/Tnn is expressed and localized along vertical myosepta and the border of the ventral neural tube during spinal motor nerve development. To assess its function, we generated a CRISPR/Cas9 mutant allele, tnnuva96, and performed in vivo imaging and morphological analysis throughout motor nerve development. Loss of tnn leads to a subtle and transient increase in ectopic motor axon exit and aberrant motor axon branching in the zebrafish trunk. Our findings reveal a previously unrecognized role for tnn in spinal motor nerve assembly and expand our understanding of the diverse molecular contributors to spinal motor nerve development and morphogenesis.

developmental biology↗

bioRxiv2025

Endothelial Adgrl2 expression and alternative splicing controls the cerebrovasculature

Central nervous system development requires parallel but interrelated processes of neural circuit assembly and vascularization. Intersecting between these two processes, the cell-adhesion G-protein coupled receptor Adgrl2 is expressed in select neuron populations where it has been found to localize and control the assembly of specific synaptic sites. Further, Adgrl2 is found to be expressed in select non-neuronal brain cells, where it is restricted to endothelial cells. Testing for Adgrl2 function in these cells, here we find that endothelial cell specific Adgrl2 deletion results in an impairment in cerebrovascular integrity. To understand how it might be possible for Adgrl2 to function independently in neuronal and endothelial contexts, we analyzed single-cell RNA sequencing datasets for differences in transcriptional identity between these cell classes. Doing so, we find that expression of Adgrl2 mRNA is subject to robust cell type-specific alternative splicing, resulting in distinct isoforms being produced in neurons compared to endothelial cells. Investigating the functional implication of this cell type-specific alternative splicing, we find that forced expression of the neuronal isoform of Adgrl2 in endothelial cells leads to alterations in cerebrovascular properties. Morphologically, endothelial cells with the non-native neuronal Adgrl2 isoform induce the formation of ectopic glutamatergic synaptic contacts onto endothelial cells, indicating alterations in the cell-cell recognition process. Functionally, in direct contrast to endothelial Adgrl2 deletion, this genetic expression switch instead enhances blood-brain barrier integrity. This overly restrictive cerebrovascular function results in dysregulation of blood to cerebrospinal fluid homeostasis, enlargement of brain ventricles, and a higher risk of hydrocephalus. As such, alternative splicing serves as a cell type specific mechanism that provides isoform specific Adgrl2 for discerning functions controlling neural circuit assembly and cerebrovascular homeostasis.

neuroscience↗

bioRxiv2021

Non-Canonical Projections from Ventral CA1 and Subicular Complex to CA3 Augments the Feedforward Hippocampal Trisynaptic Pathway

The hippocampal formation is well documented as having a feedforward, unidirectional circuit organization termed the trisynaptic pathway. This circuit organization exists along the septotemporal axis of the hippocampal formation, but the circuit connectivity across septal to temporal regions is less well described. The emergence of viral-genetic mapping techniques enhances our ability to determine the detailed complexity of hippocampal formation circuitry. In earlier work, we mapped a subiculum back-projection to CA1 prompted by the discovery of theta wave back-propagation from the subiculum to CA1 and CA3. We reason that this circuitry may represent multiple extended non-canonical pathways involving the subicular complex and hippocampal subregions CA1 and CA3. In the present study, multiple retrograde viral tracing approaches produced robust mapping results, which supports this prediction. We find significant non-canonical synaptic inputs to dorsal hippocampal CA3 from ventral CA1, perirhinal cortex, and the subicular complex. Thus, CA1 inputs to CA3 run opposite the trisynaptic pathway and in a temporal to septal direction. Our retrograde viral tracing results are confirmed by anterograde-directed viral mapping of projections from input mapped regions to hippocampal dorsal CA3. Together, our data provide a circuit foundation to explore novel functional roles contributed by these non-canonical hippocampal circuit connections to hippocampal dynamics and behavior.

neuroscience↗