Biology subjects

Ayers, K.

Publications and source records attributed to Ayers, K..

4 recordsLinked to original sources

bioRxiv2025

Examination of germline and somatic intercellular bridges in Hydra vulgaris reveals insights into the evolutionarily conserved mechanism of intercellular bridge formation

Incomplete cytokinesis results in the formation of stable intercellular bridges that have been extensively studied in bilaterians, where they play essential roles in cell-cell communication and coordination of differentiation. However, little is known about their structure and molecular composition in non-bilaterian animals. This study characterizes germline and somatic intercellular bridges in the cnidarian Hydra vulgaris, providing insights into their evolutionary origins and functional significance. We identified key conserved components, including KIF23, F-actin, and phosphotyrosine. Notably, we observed microtubule localization within Hydra ring canals, suggesting previously unrecognized functions for this cytoskeletal component in intercellular bridge formation. Bioinformatic analyses confirmed the conserved expression of Kif23 and suggested its role as a molecular marker for identifying ring canal-associated components. EdU incorporation during DNA replication demonstrated that cells connected by ring canals exhibit synchronized cell cycles, which may be critical for the coordination of division and differentiation. Our findings reveal that the molecular and structural features of intercellular bridges in Hydra are conserved across evolutionary lineages, highlighting their ancient origins and functional significance in cellular connectivity. The presence of synchronized cell cycles in ring canal-connected cells underscores their role in promoting coordinated cellular behaviors, processes fundamental to multicellular organization. This study provides new perspectives on the evolution of incomplete cytokinesis and establishes a framework for comparative investigations into the diversity and conservation of intercellular bridge mechanisms across metazoans.

cell biology↗

bioRxiv2022

Functional genomics analysis identifies impairment of HNF1B function as a cause of Mayer-Rokitansky-Küster-Hauser syndrome.

Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is a congenital condition characterized by aplasia or hypoplasia of the uterus and vagina in women with a typical 46,XX karyotype. This condition can occur as type I when isolated or as type II when associated with extragenital anomalies including kidney and skeletal abnormalities. The genetic basis of MRKH syndrome remains unexplained and several candidate genes have been proposed to play a role in its etiology, including HNF1B, LHX1, and WNT4. Here, we conducted a genomic analysis of 13 women affected by MRKH syndrome, resulting in the identification of candidate genes, including several novel candidates. We focused on HNF1B for further investigation due to its known association with, but unknown etiological role in, MRKH syndrome. We ablated Hnf1b specifically in the epithelium of the Mullerian ducts in mice, and found that this caused hypoplastic development of both the epithelial and stromal compartments of the uterus, as well as kidney anomalies, closely mirroring the MRKH type II phenotype. Using single-cell RNA sequencing of uterine tissue in the Hnf1b-ablated embryos, we analyzed the molecules and pathways downstream of Hnf1b, revealing a dysregulation of processes associated with cell proliferation, migration, and differentiation. Thus, we establish that loss of Hnf1b function leads to an MRKH phenotype, and generate the first mouse model of MRKH syndrome type II. Our results support the diagnostic value of HNF1B in clinical genetic testing for MRKH syndrome, and shed new light on the genetic causes of this poorly understood condition in womens reproductive health.

developmental biology↗

bioRxiv2019

Ring canals permit extensive cytoplasm sharing among germline cells independent of fusomes in Drosophila testes

Intercellular bridges, also called ring canals (RCs), connect germline cells during gametogenesis in males and females. They form as a consequence of incomplete cytokinesis during cell division leaving groups of daughter cells connected in syncytia. In Drosophila females, RCs are required for oocyte growth but little is known about the role of RCs during spermatogenesis. Using live imaging, we document extensive intercellular movement of GFP and a subset of endogenous proteins through RCs during spermatogenesis from two-cell diploid spermatogonia to clusters of 64 post-meiotic haploid spermatids. Loss of the fusome, a large cytoplasmic structure extending through RCs that is known to be important during oogenesis, has minimal impact on RC development or intercellular protein movement during spermatogenesis. Our results reveal that male germline RCs remain persistently open and mediate extensive sharing of cytoplasmic information, supporting multiple roles for RCs throughout sperm development.

developmental biology↗

bioRxiv2017

Modeling acute myeloid leukemia in a continuum of differentiation states

Here we present a mathematical model of movement in an abstract space representing states of cellular differentiation. We motivate this work with recent examples that demonstrate a continuum of cellular differentiation using single cell RNA sequencing data to characterize cellular states in a high-dimensional space, which is then mapped into [R]2 or [R]3 with dimension reduction techniques. We represent trajectories in the differentiation space as a graph, and model directed and random movement on the graph with partial differential equations. We hypothesize that flow in this space can be used to model normal differentiation processes as well as predict the evolution of abnormal differentiation processes such as those observed during pathogenesis of acute myeloid leukemia (AML).

cancer biology↗