Biology subjects

Sanders, T. A.

Publications and source records attributed to Sanders, T. A..

2 recordsLinked to original sources

bioRxiv2025

Exosome secretion is required for sonic hedgehog dispersal and signal gradient formation in the embryonic limb mesenchyme

Carrier-assisted diffusion and cytoneme transport have been postulated to disperse Hedgehog across diverse embryonic tissues, yet their relative contributions to patterning mesenchymal tissues remains poorly understood. Here, we combine novel signaling assays with quantitative microscopy to establish exosome secretion as a predominant and adaptable mechanism for Sonic Hedgehog (Shh) dispersal. Introducing a novel synchronous release system to visualize Shh trafficking in embryonic tissues, we demonstrate that Shh traffics through the exosome biogenesis pathway in the limb bud mesenchyme. Shh-bound exosomes diffuse through extracellular space, and can also bind and travel along cytonemes, providing a potential mechanism for directed and/or long-range transport. Using a synthetic patterning assay, we show that exosome secretion is essential to establish short-range Shh gradients in vitro. We propose that exosome-based Shh secretion, combined with different modes of extracellular transport, provides a tunable mechanism to sculpt Shh gradients on different length and time scales, across different embryonic tissues. HIGHLIGHTSO_LIA novel synchronous release system reveals trafficking dynamics in embryonic cells C_LIO_LISonic hedgehog is packaged and secreted on exosomes for extracellular dispersal C_LIO_LIExosome secretion is required to establish short-range Hedgehog gradients C_LIO_LIDiffusion and cytoneme transport provide tunable exosome dispersal strategies C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/692671v1_ufig1.gif" ALT="Figure 1"> View larger version (89K): org.highwire.dtl.DTLVardef@76b266org.highwire.dtl.DTLVardef@ba5b4borg.highwire.dtl.DTLVardef@bf9d67org.highwire.dtl.DTLVardef@1f6d699_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2025

Genetic regulation of fatty acid content in adipose tissue

Fatty acids are important as structural components, energy sources, and signaling mediators. While studies have extensively explored genetic regulation of fatty acids in serum and other bodily fluids, their regulation within adipose tissue, a crucial regulator of cardiovascular and metabolic health remains unclear. Here, we investigated the genetic regulation of 18 fatty acids in subcutaneous adipose tissue from 569 female twins from TwinsUK. Using twin models, the heritability of fatty acids ranged from 5% to 59%, indicating a substantial genetic regulation of fatty acid levels within adipose tissue, which was also tissue-specific in many cases. Genome-wide association studies identified ten significant loci, in SCD, ADAMTSL1, ZBTB41, SNTB1, EXOC6B, ACSL3, LINC02055, MKRN2/TSEN2, FADS1 and HAPLN across 13 fatty acids or fatty acid product-to-precursor ratios. Using adipose gene expression and methylation, which were concurrently measured in these samples, we detected five fatty acid-associated signals that colocalized with eQTL and meQTL signals, highlighting fatty acids that are regulated by molecular processes within adipose tissue. We identified strong associations of adipose fatty acids-associated loci with type 2 diabetes, body fat percentage, and cardiovascular disease. We explored links between polygenic scores of common metabolic traits and adipose fatty acid levels, and identified associations between polygenic scores of BMI, body-fat distribution and triglycerides and several fatty acids, indicating these risk scores impact local adipose tissue content. Overall, our results identified local genetic regulation of fatty acids within adipose tissue and highlighted their links with renal and cardio-metabolic health.

genetics↗