Controlling cell proliferation is critical for organism development, tissue homeostasis, disease, and regeneration. IQGAP3 has been shown to be required for proper cell proliferation and migration, and is associated to a number of cancers. Moreover, its expression is inversely correlated with the overall survival rate in the majority of cancers. Here, we show that IQGAP3 expression is elevated in cervical cancer and that in these cancers IQGAP3 high expression is correlated with an increased lethality. Furthermore, we demonstrate that IQGAP3 is a target of YAP, a regulator of cell cycle gene expression. IQGAP3 knockdown resulted in an increased percentage of HeLa cells in S phase, delayed progression through mitosis, and caused multipolar spindle formation and consequentially aneuploidy. Protein–protein interaction studies revealed that IQGAP3 interacts with MMS19, which is known in Drosophila to permit, by competitive binding to Xpd, Cdk7 to be fully active as a Cdk-activating kinase (CAK). Notably, IQGAP3 knockdown caused decreased MMS19 protein levels and XPD knockdown partially rescued the reduced proliferation rate upon IQGAP3 knockdown. This suggests that IQGAP3 modulates the cell cycle via the MMS19/XPD/CAK axis. Thus, in addition to governing proliferation and migration, IQGAP3 is a critical regulator of mitotic progression and genome stability.Implications: Our data indicate that, while IQGAP3 inhibition might be initially effective in decreasing cancer cell proliferation, this approach harbors the risk to promote aneuploidy and, therefore, the formation of more aggressive cancers.

The amputation of a teleost fin rapidly triggers an intricate maze of hierarchically regulated signalling processes which ultimately reconstruct the diverse tissues of the appendage. Whereas the generation of the fin pattern along the proximodistal axis brings with it several well‐known developmental regulators, the mechanisms by which the fin widens along its dorsoventral axis remain poorly understood. Utilizing the zebrafish as an experimental model of fin regeneration and studying more than 1000 actinopterygian species, we hypothesized a connection between specific inter‐ray regulatory mechanisms and the morphological variability of inter‐ray membranes found in nature. To tackle these issues, both cellular and molecular approaches have been adopted and our results suggest the existence of two distinguishable inter‐ray areas in the zebrafish caudal fin, a marginal and a central region. The present work associates the activity of the cell membrane potassium channel kcnk5b, the fibroblast growth factor receptor 1 and the sonic hedgehog pathway to the control of several cell functions involved in inter‐ray wound healing or dorsoventral regeneration of the zebrafish caudal fin. This ray‐dependent regulation controls cell migration, cell‐type patterning and gene expression. The possibility that modifications of these mechanisms are responsible for phenotypic variations found in euteleostean species, is discussed.

Adhesion G protein-coupled receptors (aGPCRs) comprise the second-largest class of GPCRs, the most common target for approved pharmacological therapies. aGPCRs play an important role in development and disease and have recently been associated with the kidney. Several aGPCRs are expressed in the kidney and some aGPCRs are either required for kidney development or their expression level is altered in diseased kidneys. Yet, general aGPCR function and their physiological role in the kidney are poorly understood. Here, we characterize in detail Gpr126 (Adgrg6) expression based on RNAscope^® technology in zebrafish, mice, and humans during kidney development in adults. Gpr126 expression is enriched in the epithelial linage during nephrogenesis and persists in the adult kidney in parietal epithelial cells, collecting ducts, and urothelium. Single-cell RNAseq analysis shows that gpr126 expression is detected in zebrafish in a distinct ionocyte sub-population. It is co-detected selectively with slc9a3.2, slc4a4a, and trpv6, known to be involved in apical acid secretion, buffering blood or intracellular pH, and to maintain high cytoplasmic Ca²⁺ concentration, respectively. Furthermore, gpr126-expressing cells were enriched in the expression of potassium transporter kcnj1a.1 and gcm2, which regulate the expression of a calcium sensor receptor. Notably, the expression patterns of Trpv6, Kcnj1a.1, and Gpr126 in mouse kidneys are highly similar. Collectively, our approach permits a detailed insight into the spatio-temporal expression of Gpr126 and provides a basis to elucidate a possible role of Gpr126 in kidney physiology.

Crustose coralline algae (CCA) occur from the tropics to the poles in photic benthic environments. Here, we report on some of the world’s southernmost and coldest CCA sites in Terra Nova, Ross Sea, Antarctica at 74°41′ S. The recently described red alga Tethysphytum antarticum is investigated for its skeletal architecture, its mineralogical and geochemical composition, as well as for its taxonomic classification. A phylogenetic analysis based on molecular genetics and the sequencing of the photosystem II protein D1 (psbA) gave a perfect match with T. antarcticum. Histological sections and micro-CT-scans provide new diagnostic details for the conceptacles (the reproductive organs of the alga). X-ray diffractometry and electron-microprobe measurements yielded a clear high-Mg calcite (~8 mol%) composition of the skeletal parts. Detailed back-scattered electron imaging of polished petrographic thin sections revealed a two-layered thallus (vegetative plant tissue), comprising an organic-rich irregularly calcified basal layer with rectangular cells, overlain by the main thallus. Elemental maps show relatively increased sulphur in the basal layer, clearly tied to organic cell walls. MgCO₃ and SrCO₃ were targeted with semiquantitative elemental mappings and in an ontogenetic quantitative spot transect. Compared with temperature (−1.95 °C to +1.08 °C), the MgCO₃ (mol%) reflects this world’s coldest CCA site temperature with the lowest MgCO₃ content of 7.9 ± 1.6 mol%. The along transect variability, however, shows with ~6 mol% a larger MgCO₃ variability than expected for the 3 °C intra-annual temperature amplitude in Terra Nova Bay. This implies that in low amplitude settings the biomineralisation control on Mg/Ca ratios can outcompete its temperature sensitivity. Mark-recapture studies, next to the environmental logger station La Zecca are suggested, to perform a detailed growth rate and biomineralisation quantification.

Uncovering the function of understudied G protein-coupled receptors (GPCRs) provides a wealth of untapped therapeutic potential. The poorly understood adhesion GPCR Gpr126 (Adgrg6) is widely expressed in developing kidneys. In adulthood, Gpr126 expression is enriched in parietal epithelial cells (PECs) and epithelial cells of the collecting duct and urothelium. Whether Gpr126 plays a role in kidney disease remains unclear. Here, we characterized Gpr126 expression in diseased kidneys in mice, rats, and humans. RT-PCR data show that Gpr126 expression is altered in kidney disease. A quantitative RNAscope^® analysis utilizing cell type-specific markers revealed that Gpr126 expression upon tubular damage is mainly increased in cell types expressing Gpr126 under healthy conditions as well as in cells of the distal and proximal tubules. Upon glomerular damage, an increase was mainly detected in PECs. Notably, Gpr126 expression was upregulated in an ischemia/reperfusion model within hours, while upregulation in a glomerular damage model was only detected after weeks. An analysis of kidney microarray data from patients with lupus nephritis, IgA nephropathy, focal segmental glomerulosclerosis (FSGS), hypertension, and diabetes as well as single-cell RNA-seq data from kidneys of patients with acute kidney injury and chronic kidney disease indicates that GPR126 expression is also altered in human kidney disease. In patients with FSGS, an RNAscope^® analysis showed that GPR126 mRNA is upregulated in PECs belonging to FSGS lesions and proximal tubules. Collectively, we provide detailed insights into Gpr126 expression in kidney disease, indicating that GPR126 is a potential therapeutic target.