Biology subjects

Bearce, E. A.

Publications and source records attributed to Bearce, E. A..

3 recordsLinked to original sources

bioRxiv2025

Motile cilia spin the Reissner fiber, a tensioned and anchored extracellular thread essential for body morphogenesis

The Reissner fiber (RF) is an extracellular thread composed of the glycoprotein SCO-spondin (Sspo) that forms within cerebrospinal fluid (CSF) in the brain ventricles and central canal (CC) of vertebrates. Its assembly depends on motile cilia, yet how cilia and CSF flow transform secreted Sspo into a fiber that spans the length of the body axis has remained unknown. Using live imaging in zebrafish, we show that globular Sspo is remodeled into thin fibrils that anchor to the floor plate (FP), elongate, and spin together into a tensioned, posteriorly translocating RF. Fiber assembly draws on a shared CSF pool of Sspo but requires local ciliary activity for globule-to-fibril remodeling. Once assembled, the RF is anchored by dynamic fibrils that stabilize the fiber and preserve its tension. Perturbations that locally disrupt ciliary motility and RF integrity along the CC result in region-specific defects in axial morphogenesis. These findings identify the RF as a flow-responsive extracellular system that converts ciliary beating into mechanical structure, linking fluid dynamics to the large-scale shaping of the vertebrate body. HighlightsO_LIMotile cilia remodel Sspo globules into FP-anchored fibrils that bundle into RF. C_LIO_LIRF assembly draws on a shared CSF Sspo pool but requires local cilia activity. C_LIO_LILaser ablation reveals patterned RF tension constrained by dynamic FP anchors. C_LIO_LIRegional cilia defects cause local RF loss and corresponding body shape defects. C_LI

developmental biology↗

bioRxiv2022

Urotensin II-Related Peptides, Urp1 and Urp2, Control Zebrafish Spine Morphology

The spine provides structure and support to the body, yet how it develops its characteristic morphology as the organism grows is little understood. This is underscored by the commonality of conditions in which the spine curves abnormally such as scoliosis, kyphosis and lordosis. Understanding the origin of such spinal curves has been challenging in part due to the lack of appropriate animal models. Recently, zebrafish have emerged as promising tools with which to understand the origin of spinal curves. Using zebrafish, we demonstrate that the Urotensin II-related peptides (URPs), Urp1 and Urp2, are essential for maintaining spine morphology. Urp1 and Urp2 are 10-amino acid cyclic peptides expressed by neurons lining the central canal of the spinal cord. Upon combined genetic loss of Urp1 and Urp2, adolescent-onset planar curves manifested in the caudal region of the spine, akin to a lordosis-like condition. Highly similar curves were caused by mutation of Uts2r3, an URP receptor. Quantitative comparisons revealed that Urotensin-associated curves were distinct from other zebrafish spinal curve mutants that more closely reflected idiopathic scoliosis or kyphosis. Last, we found that the Reissner fiber, a proteinaceous thread that sits in the central canal and has been implicated in the control of spine morphology, breaks down prior to curve formation in an idiopathic scoliosis model but was unperturbed by loss of Uts2r3. This suggests a Reissner fiber-independent mechanism of curvature in Urotensin-deficient mutants. Overall, our results show that Urp1 and Urp2 control zebrafish spine morphology and establish new animal models of lordosis-like curves.

developmental biology↗

bioRxiv2021

Tacc3 modulates microtubule network dynamicity and focal adhesion remodeling to affect cranial neural crest cell migration in Xenopus laevis

Coordinated cell migration is critical during embryogenesis, as cells must leave their point of origin, navigate a complex barrage of signals, and accurately position themselves to facilitate correct tissue and organ formation. The cell motility process relies on dynamic interactions of the F-actin and microtubule (MT) cytoskeletons. Our work focuses on how one MT plus-end regulator, Transforming Acidic Coiled-Coil 3 (Tacc3), can impact migration of cranial neural crest cells in Xenopus laevis. We previously demonstrated that tacc3 expression is expressed in cranial neural crest cells, and that Tacc3 can function as a MT plus-end tracking protein to regulate MT growth velocities. Here, we demonstrate that manipulation of Tacc3 protein levels is sufficient to alter cranial neural crest cell velocity in vitro. Tacc3 overexpression drives increased single-cell migration velocities, while Tacc3 KD results in reduced cell velocity and defective explant dispersion. We also show that Tacc3 can have spatially-enhanced effects on MT plus-end growth velocities as well as effects on focal adhesion remodeling. Together, we demonstrate that Tacc3 can facilitate neural crest cell motility through spatially-enhanced cytoskeletal remodeling, which may underlie the enhanced metastatic potential of Tacc3-overexpressing tumor cells.

cell biology↗