RT Journal Article SR Electronic T1 Accelerated cell cycles enable organ regeneration under developmental time constraints in the Drosophila hindgut JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.02.17.953075 DO 10.1101/2020.02.17.953075 A1 Erez Cohen A1 Donald T. Fox YR 2020 UL http://biorxiv.org/content/early/2020/02/17/2020.02.17.953075.abstract AB Individual organ development must be temporally coordinated with development of the rest of the organism. As a result, cell division in a developing organ occurs on a relatively fixed time scale. Despite this, many developing organs can regenerate cells lost to injury. How organs regenerate within the time constraints of organism development remains unclear. Here, we show the developing Drosophila hindgut regenerates by accelerating the mitotic cell cycle. This process requires JAK/STAT signaling and is achieved by decreasing G1 length during the normal period of developmental mitoses. Mitotic capacity is then terminated by the steroid hormone ecdysone receptor. This receptor activates a hindgut-specific enhancer of fizzy-related, a negative regulator of mitotic cyclins. We further identify the Sox transcription factor Dichaete as an important negative regulator of injury-induced mitotic cycles. Our findings reveal how mitotic cell cycle entry mechanisms can be adapted to accomplish developmental organ regeneration.