Biology subjects

Corkins, M. E.

Publications and source records attributed to Corkins, M. E..

6 recordsLinked to original sources

bioRxiv2026

Life Under Pressure: Dissection of Cross-Phyla Metazoan Responses to Extreme Hydrostatic Pressure Reveals Pressure-Protective Heat Shock Acclimation

The deepest ocean is one of the most extreme environments for life on our planet, combining near-freezing temperatures, low oxygen levels, and hydrostatic pressures reaching 111 MPa (1100 atm). Extreme pressures are predicted to alter many aspects of biology, including the physical properties of biological hydrogels, protein structure, and the solubility of gases in water. How organisms have adapted to live in these conditions is poorly understood. Studying these organisms in situ is difficult and requires specialized deep-sea equipment capable of withstanding the extreme pressure; raising these organisms in captivity is also challenging due to their extreme habitat requirements. Given these difficulties in studying deep-sea organisms, we set out to identify the problems shallow-dwelling organisms face due to increased pressure. These can provide insights into how organisms tolerate life in the deepest parts of the ocean. This project aims to take embryos of the shallow-dwelling aquatic organism Xenopus laevis, determine how surface-dwelling organisms fail under high hydrostatic pressure, and identify a means to survive this deadly pressure. We have designed a system to expose different embryonic stages of X. laevis to high pressures and observe its effects. After identifying the limits of survivability, we sought to understand how these embryos can acclimate to changing pressures. Comparative RNA-seq and cross-species analyses revealed a conserved, pressure-induced transcriptional response across phyla, with the heat shock pathway among the most strongly activated. Pre-activation of this pathway via prior pressure or other stressors enhances survival under otherwise lethal hydrostatic conditions.

evolutionary biology↗

bioRxiv2026

Dnmbp interacts with Daam1 to facilitate assembly of cadherin-mediated junctions in epithelializing nephric tubules

The mature kidney contains approximately one million nephrons, and defects arising during nephron development can result in lifelong renal impairment, often culminating in kidney failure and transplantation. Nephric tubule formation requires coordinated epithelial processes, including polarity, adhesion, signaling, and vesicle transport; however, how these processes are integrated during kidney morphogenesis remains unclear. Dynamin binding protein (Dnmbp) is a multi-domain scaffolding protein expressed in human kidneys that is involved in several cellular processes. Using the Xenopus embryonic kidney, we previously demonstrated that Dnmbp is essential for nephrogenesis, yet the mechanisms by which it influences nephron development remain undefined. Here, we identify Dnmbp as a novel interacting partner of the Wnt/planar cell polarity effector Daam1. The interaction between Daam1 and Dnmbp was independently identified in two yeast two-hybrid screens, biochemically verified, and supported by structural modeling predictions of a Daam1-Dnmbp complex. In developing Xenopus laevis kidneys, Dnmbp localized to punctate structures associated with E-cadherin-rich cell-cell contacts. Dnmbp depletion significantly reduced junctional E-cadherin localization in both epithelializing and mature nephric tubules without affecting total E-cadherin levels, indicating a role in E-cadherin recruitment or stabilization at adherens junctions. Furthermore, expression of human DNMBP rescued the junctional defects, confirming the specificity of the loss-of-function phenotype. Together, these findings identify Dnmbp as an essential regulator of kidney development and support a model in which Dnmbp provides a mechanistic link between Wnt/PCP signaling, Cdc42 activation, and adherens junction formation during nephrogenesis.

developmental biology↗

bioRxiv2025

Comparative analysis of Xenopus mesonephric transcriptomics: Conservation of the developmental lineage of nephron stages

The vertebrate kidney develops through three sequential forms: the pronephros, mesonephros, and metanephros. These three forms are composed of segmented nephrons that mediate fluid filtration and solute homeostasis. In aquatic egg-laying vertebrates such as Xenopus laevis, the mesonephros serves as the final functional renal organ, whereas in mammals it is a transient embryonic structure that precedes metanephric development. Despite its central developmental and evolutionary significance, the cellular and transcriptional organization of the mesonephric kidney remains poorly defined at single-cell resolution. Here, we mapped the cellular and transcriptional landscape of the Xenopus laevis mesonephros from NF stages 46-53 to define its composition and analyze its relationship to other kidney types. By integrating single-cell RNA sequencing with in situ hybridization, immunostaining, and functional uptake assays, we identify mesonephric nephron segments, progenitor populations, and the progressive transition from mesenchymal precursors to differentiated epithelial tubules. Transcriptomic profiling of 14,411 cells reveals conserved nephron segment identities and shared differentiation programs revealed conserved nephron segment identities and a clear transition from mesenchymal progenitors to epithelialized tubules. Comparative analyses with published Xenopus pronephric and mammalian metanephric datasets identified strong transcriptional conservation between Xenopus mesonephric and mammalian metanephric nephrons. Functional assays confirmed the timing of filtrate uptake, marking the onset of renal function during metamorphosis. Together, these findings provide the first comprehensive single-cell map of Xenopus mesonephric development, demonstrating that the mechanisms of nephron patterning and differentiation are conserved across vertebrate kidney forms. This work establishes the Xenopus mesonephros as a robust model for studying vertebrate kidney development and evolutionary transitions among nephron types.

developmental biology↗

bioRxiv2022

A comparative study of cellular diversity between the Xenopus pronephric and mouse metanephric nephron

The kidney is an essential organ that ensures bodily fluid homeostasis and removes soluble waste products from the organism. The functional units within the kidneys are epithelial tubules called nephrons. These tubules take in filtrate from the blood or coelom and selectively reabsorb nutrients through evolutionarily conserved nephron segments, leaving waste product to be eliminated in the urine. Genes coding for functional transporters are segmentally expressed, enabling nephrons to function as selective filters. The developmental patterning program that generates these segments is of great interest. The Xenopus embryonic kidney, the pronephros, has served as a valuable model to identify genes involved in nephron formation and patterning. Prior work has defined the gene expression profiles of Xenopus epithelial nephron segments via in situ hybridization strategies, but our understanding of the cellular makeup of the Xenopus pronephric kidney remains incomplete. Here, we scrutinize the cellular composition of the Xenopus pronephric nephron through comparative analyses with previous Xenopus studies and single-cell mRNA sequencing of the adult mouse kidney, this study reconstructs the cellular makeup of the pronephric kidney and identifies conserved cells, segments, and expression profiles. The data highlight significant conservation in podocytes, proximal and distal tubule cells and divergence in cellular composition underlying the evolution of the corticomedullary axis, while emphasizing the Xenopus pronephros as a model for physiology and disease. Summary StatementAssessment of the conservation of gene expression between functional Xenopus laevis pronephric and mouse metanephric nephrons through single-cell RNA sequencing.

evolutionary biology↗

bioRxiv2020

Cell-Cell Adhesion During Nephron Development Is Driven by Wnt/PCP Formin Daam1

E-cadherin junctions facilitate the assembly and disassembly of cell-cell contacts that drive development and homeostasis of epithelial tissues. The stability of E-cadherin-based junctions highly depends on their attachment to the actin cytoskeleton, but little is known about how the assembly of junctional actin filaments is regulated. Formins are a conserved group of proteins responsible for the formation and elongation of filamentous actin (F-actin). In this study, using Xenopus embryonic kidney and Madin-Darby canine kidney (MDCK) cells, we investigate the role of the Wnt/ planar cell polarity (PCP) formin protein Daam1 (Dishevelled-associated activator of morphogenesis 1) in regulating E-cadherin based intercellular adhesion. Using live imaging we show that Daam1 localizes to newly formed cell-cell contacts in the developing nephron. Furthermore, analyses of junctional F-actin upon Daam1 depletion indicate a decrease in microfilament localization and their slowed turnover. We also show that Daam1 is necessary for efficient and timely localization of junctional E-cadherin, which is mediated by Daam1s formin homology domain 2 (FH2). Finally, we establish that Daam1 signaling is essential for promoting organized movement of renal cells. This study demonstrates that Daam1 formin junctional activity is critical for epithelial tissue organization.

developmental biology↗

bioRxiv2019

The Role of the Wnt/PCP Formin Daam1 in Renal Ciliogenesis

Kidneys are composed of numerous ciliated epithelial tubules called nephrons. Each nephron functions to reabsorb nutrients and concentrate waste products into urine. Defects in primary cilia are associated with abnormal formation of nephrons and cyst formation in a wide range of kidney disorders. Previous work in Xenopus laevis and zebrafish embryos established that loss of components that make up the Wnt/PCP pathway, Daam1 and ArhGEF19 (wGEF) perturb kidney tubulogenesis. Dishevelled, which activates both the canonical and non-canonical Wnt/PCP pathway, affect cilia formation in multiciliated cells. In this study, we investigated the role of the noncanoncial Wnt/PCP components Daam1 and ArhGEF19 (wGEF) in renal ciliogenesis utilizing polarized mammalian kidney epithelia cells (MDCKII and IMCD3) and Xenopus laevis embryonic kidney. We demonstrate that knockdown of Daam1 and ArhGEF19 in MDCKII and IMCD3 cells leads to loss of cilia, and Daam1s effect on ciliogenesis is mediated by the formin-activity of Daam1. Moreover, Daam1 co-localizes with the ciliary transport protein IFT88. Interestingly, knocking down Daam1 in Xenopus kidney does not lead to loss of cilia. This data suggests a new role for Daam1 in the formation of primary cilia.

molecular biology↗