TARGETED GENE DISRUPTION REVEALS THE AUTOSOMAL GSDF AS A MALE SEX INITIATOR IN MEDAKA

Abstract

SEX IS PIVOTAL FOR REPRODUCTION, EVOLUTION AND HEALTHCARE. IN THE FISH MEDAKA, THE Y-CHROMOSOMAL DMY (ALSO DMRT1BY) ACTS AS THE MALE SEX DETERMINER, WHICH ACTIVATES DMRT1 FOR MALE SEX MAINTENANCE. HOWEVER, HOW DMY MAKES THE PRIMARY MALE DECISION VIA INITIATING TESTICULAR DIFFERENTIATION HAS REMAINED UNKNOWN, AS DMY MAY BE PARADOXICALLY DISPENSABLE FOR MALENESS. HERE I REPORT THAT THE AUTOSOMAL GSDF ACTS AS A MALE SEX INITIATOR. GENE ADDITION AND DISRUPTION REVEALED THAT GSDF WAS NECESSARY AND SUFFICIENT FOR MALENESS VIA INITIATING TESTICULAR DIFFERENTIATION. INTERESTINGLY, GSDF IS A DIRECT TARGET OF DMY FOR TRANSCRIPTIONAL ACTIVATION. THEREFORE, THE AUTOSOMAL GSDF SERVES A MALE SEX INITIATOR. CONSEQUENTLY, DMY MAKES THE MALE DECISION THROUGH ACTIVATING THE MALE SEX INITIATOR GSDF AND THE MALE SEX MAINTAINER DMRT1 WITHOUT ITS OWN PARTICIPATION IN THE PROCESSES OF SEX DIFFERENTIATION AND MAINTENANCE. THIS FINDING PROVIDES NEW INSIGHTS INTO MOLECULAR MECHANISMS UNDERLYING SEX DEVELOPMENT