hox10 genes function in kidney development in the differentiation and integration of the cortical stromahox10基因在肾脏功能发展的分化和整合的皮层基质.pdfVIP

Hox10 Genes Function in Kidney Development in the Differentiation and Integration of the Cortical Stroma 1¤ 1 2 2,3 1 Alisha R. Yallowitz , Steven M. Hrycaj , Kieran M. Short , Ian M. Smyth , Deneen M. Wellik * 1 Department of Internal Medicine, Division of Molecular Medicine and Genetics University of Michigan, Ann Arbor, Michigan, United States of America, 2 Department of Biochemistry and Molecular Biology, Monash University, Clayton Campus, Melbourne, Victoria, Australia, 3 Department of Anatomy and Developmental Biology, Monash University, Clayton Campus, Melbourne, Victoria, Australia Abstract Organogenesis requires the differentiation and integration of distinct populations of cells to form a functional organ. In the kidney, reciprocal interactions between the ureter and the nephrogenic mesenchyme are required for organ formation. Additionally, the differentiation and integration of stromal cells are also necessary for the proper development of this organ. Much remains to be understood regarding the origin of cortical stromal cells and the pathways involved in their formation and function. By generating triple mutants in the Hox10 paralogous group genes, we demonstrate that Hox10 genes play a critical role in the developing kidney. Careful examination of control kidneys show that Foxd1-expressing stromal precursor cells are first observed in a cap-like pattern anterior to the metanephric mesenchyme and these cells subsequently integrate posteriorly into the kidney periphery as development proceeds. While the initial cap-like pattern of Foxd1-expressing cortical stromal cells is unaffected in Hox10 mutants, these cells fail to become properly integrated into the kidney, and do n