LB1603 Centrosomes are required for the normal development of the skin epithelium

Abstract

The skin epidermis has a stereotypical developmental and stratification program with specific cell division paradigms that may dictate progenitor cell fate. Centrosomes, the major microtubule organizing centers of animal cells, organize mitotic spindle microtubules and regulate cell division. During interphase and in differentiated cells, centrosomes provide the essential template for cilia. The functions of centrosomes during epidermal development have not been defined. In order to genetically determine and delineate the functions of mammalian centrosomes and cilia, we have conditionally removed Sas-4, which is essential for centrosome formation, or Ift88, which is essential for cilia but not centrosome formation, in the developing mouse skin epithelium. Our data showed that the skin epidermis without SAS-4 and centrosomes lacked cilia and was thinner with arrested hair follicle development at morphogenesis. As we have shown previously in the mouse embryo and developing brain, the loss of SAS-4/centrosomes led to a marked upregulation of p53 accompanied by cell death as early as embryonic day (E) 12.5; however, the differentiation process of the developing epidermis was not majorly affected. Interestingly, the removal of p53 in the SAS-4/centrosome-deficient epidermis was sufficient to rescue the epidermal and hair follicle defects but not the loss of cilia. The phenotype observed upon centrosome removal was also not due to the secondary loss of cilia because an IFT88/cilia epidermal knockout did not show overt developmental phenotypes. We conclude that in contrast to cilia, centrosomes in the epidermis are essential to ensure proper epidermal and hair follicle development in a p53-dependent manner.