Regulation Of Spindle Orientation By The Microtubule-Binding Protein ENKD1

Precise regulation of the mitotic spindle is critical for the fidelity of cell division.The mitotic spindle is a microtubule-based cellular structure that plays an essential role in cell division.Therefore,the regulation of microtubules in spindle behavior is of great importance to cell division.Microtubules are well known as a major cytoskeletal component of eukaryotes,and they are highly dynamic structures composed of ??-tubulin heterodimers.Microtubules play an important role in various cellular activities such as cell shaping,motility,division,intracellular transport,and signal tranduction.The dynamics and functions of microtubules are mainly regulated by microtubule-binding proteins and post-translational modifications of tubulin.The epidermis is an important part of the first line of defense in the body and plays a critical role in the defense against foreign harmful substances and protection of the internal environment.Epidermal cells are derived from the division and differentiation of keratinocytes in the basal layer.In this study,we first analyzed the expression of differentially expressed genes before and after basal keratinocytes division in mice by transcriptome sequencing,suggesting that ENKD1 plays a role in epidermal basal cell division.Subsequently,we constructed mice with epidermal specific ENKD1 gene knockout successfully.By analyzing the phenotypic characteristics of mice,we found that specific deletion of ENKD1 in the epidermis would affect the development of the epidermis,resulting in mice with skin functional defects.We demonstrate that knockout of ENKD1 in basal keratinocytes leads to changes in skin permeability and disrupts the barrier function of the epidermis.The effect of ENKD1 on epidermal development depends on the direction of the division of basal keratinocytes.In view of the important role for the direction of cell division in epithelial cells and nerve cells,our findings are helpful for further investigation of the morphologenesis and maintenance of other epithelial tissues,as well as the development and function of the nervous system.In addation,by analyzing the functions of ENKD1 in the process of mitosis,we demonstrate that ENKD1 is critically involved in the regulation of the direction of cell division by its role in spindle orientation.Spindle orientation is important for the distribution of cell fate determinants during cell division.There is accumulating evidence showing that the direction of cell division modulates cell fate and tissue morphogenesis;during cell division,spindle orientation is critical for the even distribution of the cytoplasm between the two daughter cells.Through quantitative analysis of the spindle,our study shows that ENKD1 plays an important role in the regulation of astral microtubules.ENKD1 stabilizes astral microtubules and regulates their dynamics.Precise regulation of this process plays a very important role in maintaining tissue homeostasis and functions.Taken together,we demonstrate that ENKD1 regulates microtubule dynamics and spindle orientation and plays an important role in the development of skin epidermal tissues.These findings are helpful for understanding the molecular mechanisms of skin development and the pathogenesis of various skin diseases.