A working model demonstrating the involvement of ethylene pathway in sex determination in Cucurbitaceae species. At different flowering stages, ACS1G, which only presented in cucumber, and ACS11 synergistically with ACO2 to produce endogenous ethylene, which suppresses WIP1 expression. WIP1 can inhibit carpel development by repressing the ACS2/ACS7 expression, which in turn inhibits stamen development. To amplify enough ethylene for the arrest of stamen primordia development, ERF31 and ERF110 mediate the positive feedback regulation via directly activating the transcription of ACS2/ACS7 and ACS11, respectively. The transcription factor genes CRC and HB40 act as carpel initiator and stamen inhibitor at the downstream of WIP1 and EIN3/EIL1, respectively. The accumulation of WIP1 and CRC transcripts are associated with the ethylene-mediated histone methylation and deacetylation, respectively. To date, there are three locus (F/CsACS1G, M/CsACS12, A/CsACS2) and two locus (A/CmACS7, G/CmWIP1) controlling sex determination that have been map-cloned in cucumber and melon, respectively. The regular arrow indicates positive regulation, and the ‘T’ represents negative regulation. The red arrow indicates positive feedback regulation.