| First Author | Jun HJ | Year | 2014 |
| Journal | Endocrinology | Volume | 155 |
| Issue | 9 | Pages | 3661-73 |
| PubMed ID | 24971615 | Mgi Jnum | J:211844 |
| Mgi Id | MGI:5576776 | Doi | 10.1210/en.2014-1341 |
| Citation | Jun HJ, et al. (2014) ROS1 Signaling Regulates Epithelial Differentiation in the Epididymis. Endocrinology :en20141341 |
| abstractText | The initial segment (IS) of the epididymis plays an essential role in male fertility. The IS epithelium is undifferentiated and non functional at birth. Prior to puberty, the epithelium undergoes differentiation, which leads to the formation of a fully functional organ. However, the mechanistic details of this program are not well understood. To explore this further, we used genetic engineering to create a kinase dead allele of the ROS1 receptor tyrosine kinase in mice and study the effects of ROS1 tyrosine kinase activity on the differentiation of the initial segment (IS) epithelium. We show that the expression and activation of ROS1 coincides with the onset of differentiation and is exclusively located in the initial segment of the maturing and adult mouse epididymides. Here we demonstrate that the differentiation of the IS is dependent on the kinase activity of ROS1 and its downstream effector MEK1/2-ERK1/2 signaling axis. Using genetic engineering, we show that germ line ablation of ROS1 kinase activity leads to a failure of the IS epithelium to differentiate, and as a consequence, sperm maturation and infertility were dramatically perturbed. Pharmacological inhibition of ROS1 kinase activity in the developing epididymis, however, only delayed differentiation transiently and did not result in infertility. Our results demonstrate that ROS1 kinase activity and the ensuing MEK1/2-ERK1/2 signaling are necessary for the postnatal development of the IS epithelium and that a sustained ablation of ROS1 kinase activity within the critical window of terminal differentiation abrogate the function of the epididymis and leads to sterility. |
