Biology subjects

Kong, S.

Publications and source records attributed to Kong, S..

3 recordsLinked to original sources

bioRxiv2018

Deletion of YAP/TAZ in mouse neocortex impaired the proliferation and differentiation ability of neural progenitor cells

YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) are downstream effectors of the Hippo pathway, they activate the expression of transcriptional targets that promote cell growth, cell proliferation, and prevent apoptosis. Here I examined the function of YAP/TAZ in mouse neocortex development through conditional deletion of Yap and Taz by Emx1-Cre. Loss of YAP/TAZ cause the hydrocephalus after birth, leads to aberrant development and dilated ventricle in adult stage, this phenotype can be detected as early as P0. YAP/TAZ are expressed in Sox2+ neural progenitor cells, when YAP/TAZ are deleted, the neuroepithelial cell junctions are disrupted; the numbers of Sox2+ cell and Tbr2+ cell are reduced and the ratio of tbr2/Sox2 is also reduced at E15.5. Results of cell cycle analyzing experiments display YAP/TAZ deletion increased the cell cycle exit. The improperly increased expression of Tuj1+ in progenitor cells in the YAP/TAZ deleted cortex indicates the premature of Sox2+ progenitor cells. Together, our results reveal that YAP/TAZ deletion changed the polarity of neuroepithelial cells, and increased the cell cycle exit, reduced the differentiation of Sox2+ cells into Tbr2+ cells through promoting the premature of Tuj1+ cells. These results define the functions of YAP/TAZ in keeping the cell polarity neural progenitors and ensuring their proliferation and differentiation, and also reveal the roles of YAP/TAZ in developing cortex.

neuroscience↗

bioRxiv2017

Investigation of the role of a macromolecular complex of CFTR-NHERF2-LPA2 in the fluid hemostasis and inflammatory responses in intestinal epithelial cells

CFTR is a cAMP-regulated chloride channel located in the apical surface of intestinal epithelial cells; where it forms a macromolecular complex with NHERF2 and LPA2. CFTR has been shown to play a role in the pathogenies of several types of secretory diarrheas. Inflammatory bowel disease (IBD) is a chronic condition of intestine characterized by severe inflammation and mucosal destruction, genetic analysis has shown that LPA contribute to IBD and patients of cystic fibrosis also display the phenotype of diarrhea. The purpose of this study is to investigate if this complex plays a role in the inflammatory responses of intestinal epithelium.\n\nWe then explored the role of this complex in maintaining the integrity of tight junction and inflammatory responses in these cells. In vitro assays show that inhibiting CFTR or LPA2 in the intestinal epithelial cell could disrupt the epithelial cell junction, and reduce the TER of intestinal epithelial cells in both mouse and human cell line. EUSA assay show that intriguing LPA2 through LPS or LPA can increase the secretion of IL-8, while inhibiting or SiRNA knockdown of LPA2 can decrease the secretion of IL-8 in mouse or human intestinal epithelial cells. The CFTR inhibitor can reduce the IL-8 secretion in both mouse and human cell line, the deletion of CFTR in mouse intestine does not affect the IL-8 level, but the knockdown of CFTR in human cell line reduced the IL-8 protein level. The deletion of CFTR in human also reduced the IL-8 mRNA level. This indicates the CFTR-LPA complex is necessary for the expression of IL-8.

pathology↗

bioRxiv2017

Dlic1 deletion impaired cerebellar development in mouse

The cerebellum is an important model system to study Central Nervous System, it has a striking morphology consisting of folia separated by fissures of different lengths, and the molecules controlling the process of cerebellar development have been unclear. In this study, we report an unrecognized contribution of Dlic1 to the postnatal development of murine cerebellum. Dlic1 encodes a light intermediate chain of cytoplasmic dynein 1, it is a subunit unique to the cytoplasmic form of dynein, and how it contributes to dynein function is not fully understood. Our data show that Dlic1 deletion leads to impaired cerebellar development, foliation and fissuration, the volume of the cerebellum was evidently reduced. Consistent with the histological defects, Dlic1 knockout mice show defective motor coordination, this strongly indicates the fundamental role of Dlic1 in cerebellar development and function. Purkinje cells are located within the cerebellum and form synapses with granule cells. In Dlic1-/- mice, Purkinje cells display reduced dendritic complexity and the distribution of dynein in Purkinje cell layer is changed. We also found that Dlic1 deletion reduced the protein levels of dynein subunits and leads to the defective assembling of dynein subunits. These data indicate that Dlic1 may affect cerebellar development through affecting the normal function of dynein.\n\nAbbreviations

neuroscience↗