During my work as a Postdoc in the lab of Brian Mitchel we showed that intracellular effectors interpret polarity to organize cellular morphology in accordance with asymmetric cellular function. We observe that both cellular actin and microtubule networks undergo drastic reorganization, providing differential roles during the polarized organization of cilia. Using computational angular correlation analysis of cilia orientation, we report a graded cellular organization downstream of cell polarity cues. Actin dynamics are required for proper cilia spacing, global coordination of cilia
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The directed movement of cells is a fundamental aspect of tissue morphogenesis. The skin of Xenopus laevis embryos represents an excellent model to study the movement of cell across epithelia. Multiciliated cells (MCCs) and ionocytes (ICs) are specialized cell types that differentiate in a subapical layer of the epidermis. These cells then move in a directed manner toward the outer epithelial cells where they undergo radial intercalation pushing through cell vertices and establishing new junctions while maintaining epithelial integrity. We identified a novel function for both the microtubule-binding protein CLAMP and members of the microtubule-regulating Par complex during intercalation.
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Multiciliated cells represent an interesting variation of centriole duplication in that these cells generate greater than 100 centrioles, which form the basal bodies of their motile cilia. This centriole amplification is proposed to require a structure termed the deuterosome, thought to be capable of promoting de novo centriole biogenesis. I contributed to the characterization of the deuterosome and identify it as a site for the
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Primary ciliary dyskinesia (PCD) is a genetic disorder in which impaired ciliary function leads to chronic airway disease. Exome sequencing of a PCD subject identified a frameshift variant that introduces a stop codon in amino acid 308 of the growth arrest-specific protein 2-like 2 (GAS2L2). In this research, using human nasal cells, mouse models, and X.laevis embryos, we show that GAS2L2 is abundant at the apical surface of ciliated cells, where it localizes with basal bodies, basal feet, rootlets, and actin filaments. Loss of GAS2L2 in mouse tracheal epithelial cell (mTEC) cultures and in X. laevis
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C21orf59/Kurly (Kur), a cytoplasmic protein with some enrichment at the base of cilia, is needed for motility, proper cilia polarization in the zebrafish kidney and the larval skin of Xenopus laevis. CRISPR/Cas9 coupled with homologous recombination to disrupt the endogenous kur locus in Xenopus resulted in the asymmetric localization of the PCP protein Prickle2 being lost in mutant multiciliated cells. Kur also makes interactions with other PCP components, including Disheveled. This supports a model wherein Kur plays a dual role in cilia motility and polarization.
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