对上皮细胞进化的新见解
Scientists of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch and the Experimental and Clinical Research Center (ECRC) of MDC and Charité in Berlin-Buch have gained new insights into the development of epithelial cells(上皮细胞) and their molecular repertoire(全部节目) . Dr. Max Werth, Katharina Walentin and Professor Kai Schmidt-Ott have identified a transcription factor (grainyhead-like 2, Grhl2), which regulates the composition of the molecular "bridges" that link adjacent(临近的,毗邻的) epithelial cells. The authors were able to demonstrate that Grhl2, via DNA-binding, directly regulates the expression of two such cell junctional molecules, E-cadherin and claudin 4 (Development, doi:10.1242/dev.055483). This could be important for understanding the mechanisms of various diseases. For example, Grhl2-deficient mice die early in embryonic development and display defects of neural tube closure, including spina bifida(脊柱裂) .
Spina bifida is a common human congenital disease(先天性疾病) that is often associated with severe disabilities. Little is known about how the disease develops, and Grhl2 may be an important player in its pathogenesis(发病机理) .
Furthermore, the authors hypothesize that Grhl2 may also have important functions in internal organs, such as the kidney. Epithelial cells line the renal(肾脏的) tubular(管状的) system, which in humans is several kilometers long.
This system of renal tubules, together with the renal corpuscles(肾小体) , forms the basic structural and functional unit of the kidney – the nephron(肾元) . The human kidney filters waste products from 1700 liters of blood per day, of which 180 liters are collected as primary urine and of which finally one to two liters are excreted as urine.
The studies of the authors show that Grhl2 is produced in nephron segments that are relatively impermeable(不渗透的) to water and solutes and that fine-tune the composition of urine.
A dysfunction of Grhl2 in these cells may affect epithelial barrier formation and other cell characteristics and, thereby, contribute to various diseases, including congenital abnormalities(畸形,机场情况) of the kidney or the development of hypertension.