Biology subjects

Heikes, K. L.

Publications and source records attributed to Heikes, K. L..

4 recordsLinked to original sources

bioRxiv2026

Hydrostatic pressure shapes and canalizes semicircular canal morphology to ensure vestibular function

How tissues acquire reproducible shapes to support their function is a fundamental question in developmental biology. Zebrafish semicircular canals form when epithelial pillars partition the lumen of the otic vesicle, the embryonic precursor of the inner ear, into the tubes that sense head rotation for balance. We show that hydrostatic pressure generated by the inflating otic vesicle shapes pillar geometry. Acute vesicle deflation shortens and broadens pillars, whereas pharmacologically induced inflation elongates and narrows them, effects captured by a physical model that treats the vesicle as a pressurized viscoelastic shell. Pillars initially form with variable curvature, but continued vesicle expansion drives them toward a common, straight geometry, a process accelerated by inflation and blocked by deflation. We identify Wnt signaling as crucial for sustaining this pressure by maintaining epithelial barrier integrity. Its disruption impairs pillar geometry and vestibular-dependent swimming behavior. Together, these findings identify hydrostatic pressure as a critical physical mechanism that canalizes tissue geometry to ensure robust organ formation and function.

developmental biology↗

bioRxiv2025

A self-limiting mechanotransduction feedback loop ensures robust organ formation

Organ morphogenesis uses mechanotransduction feedback loops to convert forces into gene expression changes that regulate cell mechanics. How these loops integrate with developmental programs to ensure robust outcomes remains unclear. We show Yap mechanotransduction establishes a self-limiting positive feedback loop for semicircular canal formation in zebrafish. Canal development proceeds through bud initiation, extension, and fusion within the otic epithelium. Local swelling of hyaluronan-rich extracellular matrix (ECM) in the bud activates Yap in a spatial pattern. Yap induces its target ccn1l1, promoting further ECM expansion to sustain bud extension. This feedback loop confers developmental robustness: graded knockdown of ccn1l1 reduces extension rate, yet canal formation persists and fails only with strong disruption. Critically, the loop contains its own termination mechanism. During bud fusion, PKA-CREB signaling, activated by an adhesion GPCR, gpr126, suppresses ccn1l1, ending the loop. These findings reveal how mechanotransduction loops with built-in termination provide developmental control by integrating mechanical forces, transcriptional responses, and morphogenetic outcomes.

developmental biology↗

bioRxiv2024

Expression patterns of FGF and BMP pathway genes in the tardigrade Hypsibius exemplaris

BackgroundA small number of signaling pathways regulates development in most animals, yet we do not know where these pathways are deployed in embryos of many animal phyla. Filling such gaps can contribute to understanding how diverse body shapes arise from differential deployment of conserved signaling pathways. Here, we examined where conserved pathways are deployed in tardigrades, a panarthropod phylum with miniaturized, segmented bodies. ResultsWe used in situ mRNA detection in the tardigrade Hypsibius exemplaris to reveal expression patterns of FGF and BMP signaling pathway components during body segmentation and early mesoderm development. Among the patterns examined, we found an FGF ligand and receptor expressed near each other in segmentally iterated regions of ectoderm and endomesoderm, respectively. We also found a BMP ligand and antagonist expressed in dorsoventrally-restricted patterns in the lateral ectoderm. ConclusionsThe detected patterns suggested specific hypotheses for further research: possible FGF signaling between ectoderm and endomesoderm, and possible roles of BMP signaling in dorsal-ventral patterning of lateral ectoderm. We compared our results with published expression patterns for FGF and BMP pathways across panarthropods, to contribute to previous hypotheses for how the development of segments and mesoderm may have evolved in the emergence of this clade of diversly-shaped animals. Bullet PointsO_LIDouble mRNA detection in tardigrades revealed expression patterns of FGF and BMP pathway genes C_LIO_LIfgf8 was detected primarily in ectoderm but absent from internal germ layers, and C_LIO_LIfgfrl1 was detected in all layers and enriched in internal layers C_LIO_LIdpp was detected more dorsally than sog in lateral ectoderm C_LIO_LIfgf8 and dpp gene expression exhibit different segmentally iterated domains in ectoderm C_LIO_LIResults suggest specific hypotheses for roles for FGF signaling and BMP signaling in tardigrade development C_LI

developmental biology↗

bioRxiv2023

The Embryonic Origin of Primordial Germ Cells in the Tardigrade Hypsibius exemplaris

Primordial germ cells (PGCs) give rise to gametes - cells necessary for the propagation and fertility of diverse organisms. Current understanding of PGC development is limited to the small number of organisms whose PGCs have been identified and studied. Expanding the field to include little-studied taxa and emerging model organisms is important to understand the full breadth of the evolution of PGC development. In the phylum Tardigrada, no early cell lineages have been identified to date using molecular markers. This includes the PGC lineage. Here, we describe PGC development in the model tardigrade Hypsibius exemplaris. The four earliest-internalizing cells (EICs) exhibit PGC-like behavior and nuclear morphology. The location of the EICs is enriched for mRNAs of conserved PGC markers wiwi1 (water bear piwi 1) and vasa. At early stages, both wiwi1 and vasa mRNAs are detectable uniformly in embryos, which suggests that these mRNAs do not serve as localized determinants for PGC specification. Only later are wiwi1 and vasa enriched in the EICs. Finally, we traced the cells that give rise to the four PGCs. Our results reveal the embryonic origin of the PGCs of H. exemplaris and provide the first molecular characterization of an early cell lineage in the tardigrade phylum. We anticipate that these observations will serve as a basis for characterizing the mechanisms of PGC development in this animal.

developmental biology↗