Evolutionary origin of the chordate nervous system revealed by amphioxus developmental trajectories.

The common ancestor of all vertebrates had a highly sophisticated nervous system, but questions remain about the evolution of vertebrate neural cell types. The amphioxus, a chordate that diverged before the origin of vertebrates, can inform vertebrate evolution. Here we develop and analyse a single-cell RNA-sequencing dataset from seven amphioxus embryo stages to understand chordate cell type evolution and to study vertebrate neural cell type origins.

Monitoring hypertensive disorders in pregnancy to prevent preeclampsia in pregnant women of advanced maternal age: Trial mimicking with retrospective data.

This study investigated the implication of monitoring hypertensive disorders in pregnancy (HDP) to prevent preeclampsia (PE) in pregnant women of advanced maternal age. Between January 2016 and April 2021, 262 consecutive pregnant women aged ≥40 years were recruited. Extensive monitoring of hypertensive disorders in pregnancy, including blood hypercoagulability screening and subsequent interventions, was performed in 129 pregnant women in our university hospital.

Liver-specific overexpression of Gab2 accelerates hepatocellular carcinoma progression by activating immunosuppression of myeloid-derived suppressor cells.

GRB2-associated-binding protein 2 (Gab2) deletion has a preventive effect of on chronic liver inflammation and hepatocellular carcinoma. This study was aimed to elaborate Gab2-initiated immunoregulation during hepatocarcinogenesis. Compared to wild-type group, liver-specific overexpression of Gab2 mice (L-Gab2) displayed early hepatocarcinogenesis after 5-month diethylnitrosamine (DEN) induction, and accelerated tumor growth after 9-month DEN challenge.

A Potential Method for Rapid Screening of Amphioxus Founder Harboring Germline Mutation and Transgene.

Amphioxus is a promising model organism for understanding the origin and evolution of vertebrates due to its basal phylogenetic position among chordates. We here compared the mutation efficacy and mutation type of tail tips and gametes of amphioxus founders injected with Cas9 protein and six different sgRNAs targeting five distinct genes, and revealed a strong correlation for mutation efficacy and a mild correlation for mutation type among the two tissues. In addition, we also observed a positive relationship between gene insertions observed in tail tips and gametes of amphioxus founders injected with Tol2 transposase and two different transgenic constructs.

Step-wise evolution of neural patterning by Hedgehog signalling in chordates.

In vertebrate embryos, Hedgehog (Hh) is expressed in some anterior basal plate domains and by notochord and floorplate cells, and ventral neural cells are patterned by the activities of Hh-regulated transcription factors. Hh signalling is antagonized by signals from the dorsal neural tube and loss of Hh leads to loss of ventral patterning as dorsal pattern expands. These mechanisms are critical for producing the neurons that implement motor responses to sensory inputs but understanding how they evolved has been hindered by lack of insight from commonly studied invertebrates where nervous system morphology and genetic mechanisms are non-conserved with vertebrates.

Mutation of amphioxus Pdx and Cdx demonstrates conserved roles for ParaHox genes in gut, anus and tail patterning.

Background: The homeobox genes Pdx and Cdx are widespread across the animal kingdom and part of the small ParaHox gene cluster. Gene expression patterns suggest ancient roles for Pdx and Cdx in patterning the through-gut of bilaterian animals although functional data are available for few lineages. To examine evolutionary conservation of Pdx and Cdx gene functions, we focus on amphioxus, small marine animals that occupy a pivotal position in chordate evolution and in which ParaHox gene clustering was first reported.

Cilia-driven asymmetric Hedgehog signalling determines the amphioxus left-right axis by controlling expression.

Cilia rotation-driven nodal flow is crucial for the left-right (L-R) break in symmetry in most vertebrates. However, the mechanism by which the flow signal is translated to asymmetric gene expression has been insufficiently addressed. Here, we show that Hedgehog (Hh) signalling is asymmetrically activated (L View Article and Find Full Text PDF

Gab2 mediates hepatocellular carcinogenesis by integrating multiple signaling pathways.

Our previous studies have found that Growth factor receptor-bound protein 2-associated binding protein 2 (Gab2)-a docking protein-governs the development of fatty liver disease. Here, we further demonstrate that Gab2 mediates hepatocarcinogenesis. Compared with a faint expression in -carcinoma tissue, Gab2 was highly expressed in ∼60-70% of human hepatocellular carcinoma (HCC) specimens.

Deletion of Gab2 in mice protects against hepatic steatosis and steatohepatitis: a novel therapeutic target for fatty liver disease.

Fatty liver disease is a serious health problem worldwide and is the most common cause for chronic liver disease and metabolic disorders. The major challenge in the prevention and intervention of this disease is the incomplete understanding of the underlying mechanism and thus lack of potent therapeutic targets due to multifaceted and interdependent disease factors. In this study, we investigated the role of a signaling adaptor protein, GRB2-associated-binding protein 2 (Gab2), in fatty liver using an animal disease model.