Biology subjects

Stenzel, A.

Publications and source records attributed to Stenzel, A..

2 recordsLinked to original sources

bioRxiv2024

Cadherin 16 promotes sensory gating via the endocrine corpuscles of Stannius

Sensory thresholds enable animals to regulate their behavioral responses to environmental threats. Despite the importance of sensory thresholds for animal behavior and human health, we do not yet have a full appreciation of the underlying molecular-genetic and circuit mechanisms. The larval zebrafish acoustic startle response provides a powerful system to identify molecular mechanisms underlying establishment of sensory thresholds and plasticity of thresholds through mechanisms like habituation. Using this system, we identify Cadherin 16 as a previously undescribed regulator of sensory gating. We demonstrate that Cadherin 16 regulates sensory thresholds via an endocrine organ, the corpuscle of Stannius (CS), which is essential in zebrafish for regulating Ca2+ homeostasis. We further show that Cadherin 16 regulates whole-body calcium and ultimately behavior through the hormone Stanniocalcin 1L, and the IGF-regulatory metalloprotease, Papp-aa. Finally, we demonstrate the importance of the CS through ablation experiments that reveal its role in promoting normal acoustic sensory gating. Together, our results uncover a previously undescribed brain non-autonomous pathway for the regulation of behavior and establish Ca2+ homeostasis as a critical process underlying sensory gating in vivo.

genetics↗

bioRxiv2022

Variable paralog expression underlies phenotype variation

Human faces are variable; we look different from one another. Craniofacial disorders further increase this variability. Here we used the zebrafish mef2ca mutant, which produces variable phenotypes, to understand craniofacial variation. Comparing different mef2ca alleles demonstrated that severity, measured by penetrance and expressivity, correlates with variation. Years of selective breeding for low and high penetrance produced strains that are either resilient, or sensitive, to the mef2ca mutation. Comparing these strains further demonstrates that severity correlates with variation. Gene expression studies indicated that selective breeding upregulated and downregulated mef2ca paralog expression in the low- and high-penetrance strains, respectively. We hypothesized that heritable paralog expression variation underlies mutant phenotype variation. In support, mutagenizing all mef2ca paralogs in the low-penetrance strain demonstrated modular buffering by paralogs. Specifically, some paralogs buffer severity while others buffer variability. We present a novel, mechanistic model for phenotypic variation where cryptic vestigial paralog expression modularly buffers development and contributes to evolution. These studies are a major step forward in understanding of the mechanisms of facial variation, including how some genetically resilient individuals can overcome a deleterious mutation.

genetics↗