The initiation of retinal development in Drosophila begins at the posterior center (PC) of the eye disc margin. The front of the differentiation wave, recognized as a morphogenetic furrow (MF), moves from posterior to anterior. What determines MF initiates from the specific PC site is still unclear. The unpaired (upd) gene is expressed at PC at early third instar, just before the time of MF initiation. Therefore, upd is expressed at the appropriate time and location for a specific role in defining the site of MF initiation. upd encodes a ligand for the Jak/STAT signaling pathway. In this report, we showed that the Upd/Jak/STAT signaling is required and sufficient to determine MF initiation. This is primarily achieved by repressing the transcription of wingless (wg), which is known to block MF initiation.