Biology subjects

Descoteaux, A. E.

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

6 recordsLinked to original sources

bioRxiv2026

Cell-specific roles for the conserved Galpha chaperone RIC-8 in cilia biology

Primary cilia exhibit conserved organization and contain structural and functional domains of unique molecular composition. The inversin compartment (InvC), which is found in the proximal ciliary segment of a subset of vertebrate and invertebrate cell types, concentrates different classes of signaling molecules. Mutations in genes encoding resident proteins of the InvC manifest in ciliopathies, highlighting the importance of the InvC in cilia biology. We previously showed that a chaperone of G proteins RIC-8 localizes to the InvC of C. elegans channel cilia; however, the mechanisms that regulate RIC-8 targeting to this ciliary sub-domain or RIC-8 function in the InvC remain unknown. Here, we build on our prior work to demonstrate that RIC-8 becomes restricted to the InvC during larval development and show that, while the RVxP motif and intact transition zone are required for its proper intraciliary distribution, RIC-8 localization to the cilium depends on intraflagellar transport. Using the ASH neuron as a model, we establish that RIC-8 modulates chemosensory responses mediated by channel cilia. Finally, we show that human RIC8A and RIC8B proteins are required for ciliogenesis in RPE-1 cells. Collectively, our results define ciliary trafficking mechanisms and novel functions for a highly conserved signaling protein.

cell biology↗

bioRxiv2025

Alizarin red perturbs skeletal patterning and biomineralization via Catalase inhibition

Alizarin Red S (AZ) is an anthraquinone dye that is commonly used in histological studies and textiles. Exposure to AZ results in morphological perturbations in several species, including rats, frogs, and dogs; however, the mechanisms by which AZ has these effects is largely unexplored, and little is known about its effect on development. We have previously shown that AZ is teratogenic to sea urchin larvae, and that AZ was the only calcium-binding mineralization marker among five tested that perturbed skeletal patterning. Here, we further characterize these defects and demonstrate that embryos exposed to AZ have abnormal skeletal element rotation, branching, and bending. Immunostains and polychrome labeling reveal delayed migration of primary mesenchyme cells and initiation of biomineralization. Although gross ectodermal dorsal-ventral specification, ciliary band restriction, and neuronal specification occur normally in the majority of AZ-treated embryos, we find abnormal patterning and connectivity of the serotonergic neurons. Temporal transcriptomics comparisons confirm delayed development and implicate changes in neuron-related GO terms with AZ treatment. Particle imaging velocimetry experiments show that ciliary beating normally directs fluid flow into the larval mouth, while AZ treatment perturbs the normal pattern of vortices and redirects flow away from the mouth. These changes in fluid flow have functional consequences for larval feeding behaviors in AZ-treated embryos. Finally, we show that the effects of AZ on skeletal patterning are largely due to its inhibition of catalase and subsequent elevation of reactive oxygen species. Specifically, catalase knockdown and transient hydrogen peroxide treatment are each sufficient to phenocopy the hallmark AZ-mediated skeletal patterning defects. This study is the first to define the teratogenic consequences of AZ exposure and show how its effects on catalase activity impact development, skeletal patterning, and biomineralization. Summary StatementAlizarin Red exposure produces teratogenic effects on skeletal and nervous systems primarily via catalase inhibition.

developmental biology↗

bioRxiv2024

PFAS Compounds PFOA and Gen X are Teratogenic to Sea Urchin Embryos

Per-and polyfluorinated substances (PFAS) are synthetic chemicals that are used to make fluoropolymer coatings found in many products, such as non-stick pans, clothing, cosmetics, and food packaging. These highly persistent molecules are known as "forever chemicals" since they neither degrade environmentally nor break down enzymatically within biological systems. PFAS compounds readily contaminate water sources, and as a result, certain PFAS molecules have bioaccumulated in exposed species including humans. The purpose of this study was to define the effect of two PFAS molecules, the ostensibly more toxic perfluorooctanoic acid (PFOA) and the more recent, reportedly safer chemical hexafluoropropylene oxide dimer acid (Gen X), on the development of Lytechinus variegatus sea urchin embryos. We examined the effects of PFOA and Gen X on development and patterning using morphological analysis, immunostaining, HCR-FISH, and Particle Image Velocimetry (PIV). The results show that both PFAS compounds are teratogenic to sea urchin embryos. PFOA and Gen X each function at different intervals during development and provoke distinct phenotypic and gene expression outcomes. Despite beliefs that Gen X would be a safer alternative, our findings indicate that Gen X has earlier and more severe effects on endomesoderm and dorsal-ventral axis specification, neural development and function, and pattern formation compared to PFOA. These results illustrate the dangerous teratogenic potential of environmentally accumulating PFAS like Gen X, underscoring the negative ecological implications that accompany continuing commercial and industrial use of PFAS in the absence of remediation strategies. HIGHLIGHTSO_LIGen X is more teratogenic in sea urchins than PFOA C_LIO_LIGen X acts earlier than PFOA and perturbs axial and germ layer specification C_LIO_LIEach PFAS reduces neural numbers and perturbs ciliary behavior and swimming C_LI

developmental biology↗

bioRxiv2024

CMTM4 is an adhesion modulator that regulates skeletal patterning and primary mesenchyme cell migration in sea urchin embryos

MARVEL proteins, including those of the CMTM gene family, are multi-pass transmembrane proteins that play important roles in vesicular trafficking and cell migration; however, little is understood about their role in development, and their role in skeletal patterning is unexplored. CMTM4 is the only CMTM family member found in the developmental transcriptome of the sea urchin Lytechinus variegatus. Here, we validate that LvCMTM4 is a transmembrane protein and show that perturbation of CMTM4 expression via zygotic morpholino or mRNA injection perturbs skeletal patterning, resulting in loss of secondary skeletal elements and rotational defects. We also demonstrate that normal levels of CMTM4 are required for normal PMC migration and filopodial organization, and that these effects are not due to gross mis-specification of the ectoderm. Finally, we show that CMTM4 is sufficient to mediate PMC cell-cell adhesion. Taken together, these data suggest that CMTM4 controls PMC migration and biomineralization via adhesive regulation during sea urchin skeletogenesis. This is the first discovery of a functionally required adhesive gene in this skeletal patterning system. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=163 SRC="FIGDIR/small/616569v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@b5564borg.highwire.dtl.DTLVardef@1347616org.highwire.dtl.DTLVardef@134d970org.highwire.dtl.DTLVardef@af863a_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2022

Polychrome labeling reveals skeletal triradiate and elongation dynamics and abnormalities in patterning cue-perturbed embryos

The larval skeleton of the sea urchin Lytechinus variegatus is an ideal model system for studying skeletal patterning; however, our understanding of the etiology of skeletal patterning in sea urchin larvae is limited due to the lack of approaches to live-image skeleton formation. Calcium-binding fluorochromes have been used to study the temporal dynamics of bone growth and healing. To date, only calcein green has been used in sea urchin larvae to fluorescently label the larval skeleton. Here, we optimize labeling protocols for four other calcium-binding fluorochromes-alizarin red, xylenol orange, tetracycline, and calcein blue- and demonstrate that these fluorochromes can be used individually or in nested pulse-chase experiments to understand the temporal dynamics of skeletogenesis and patterning. Using this pulse-chase approach we reveal that the initiation of skeletogenesis begins around 15 hours post fertilization, which is earlier than previously thought. We also explore the timing of triradiate formation in embryos treated with a range of patterning perturbagens, and demonstrate that triradiates form late and asynchronously in embryos ventralized via treatment with either nickel at early gastrula stage or with chlorate from fertilization. Finally, we measure the extent of fluorochrome incorporation in triple-labeled embryos to determine the elongation rate of numerous skeletal elements throughout early skeletal patterning and compare this to the rate of skeletal growth in axitinib-treated embryos. We find that skeletal elements elongate much more slowly in axitinib-treated embryos, and that axitinib treatment is sufficient to induce abnormal orientation of the triradiates. HighlightsO_LICalcium-binding fluorochromes selectively label the sea urchin larval skeleton C_LIO_LIPulsed, nested polychrome labeling offers temporal insight into skeletal patterning C_LIO_LITriradiate formation is delayed and asynchronous in ventralized embryos C_LIO_LIVEGFR inhibition slows skeletal elongation and perturbs triradiate orientation C_LI

developmental biology↗

bioRxiv2019

Mad dephosphorylation at the nuclear envelope is essential for asymmetric stem cell division

Stem cell niche signals act over a short range so that only stem cells but not the differentiating daughter cells receive the self-renewal signals. Drosophila female germline stem cells (GSCs) are maintained by short range BMP signaling; BMP ligands Dpp/Gbb activate receptor Tkv to phosphorylate Mad (phosphor-Mad or pMad) which accumulates in the GSC nucleus and activates the stem cell transcription program. pMad is highly concentrated in the nucleus of the GSC, but is immediately downregulated in the nucleus of the pre-cystoblast (preCB), a differentiating daughter cell, that is displaced away from the niche. Here we show that this asymmetry in the intensity of pMad is formed even before the completion of cytokinesis. A delay in establishing the pMad asymmetry leads to germline tumors through conversion of differentiating cells into a stem cell-like state. We show that a Mad phosphatase Dullard (Dd) interacts with Mad at the nuclear pore, where it may dephosphorylate Mad. A mathematical model explains how an asymmetry can be established in a common cytoplasm. It also demonstrates that the ratio of pMad concentrations in GSC/preCB is highly sensitive to Mad dephosphorylation rate. Our study reveals a previously unappreciated mechanism for breaking symmetry between daughter cells during asymmetric stem cell division.

developmental biology↗