EFNB2 and Prader-Willi syndrome: Both EphB1 forward and EfnB2 reverse signaling can activate MAPK pathways, which leads to a reasonable speculation that the upregulation of MAPK pathways is due to co-expression of EphB1 and EfnB2 in PWS ECs; and (4) genetic somatic mutations, such as RASA1 and GNAQ, which will be discussed below.