Accelerated cell cycles enable organ regeneration under developmental time constraints in theDrosophilahindgut

Abstract

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.

Ecdysone exerts biphasic control of regenerative signaling, coordinating the completion of regeneration with developmental progression

“…Similarly, recently published experiments have observed that damage of the Drosophila hindgut during L2 or early L3 produces Dilp8, delaying the onset of pupariation, whereas damage to the hindgut of wandering L3 larvae no longer produces Dilp8 or developmental delay. However, regeneration is still completed in this attenuated period through accelerated mitotic cycling, which allows the tissue to meet the regeneration target within the mitotic regeneration window (Cohen et al, 2021). In this example, while ecdysone signaling regulates the end of mitotic regeneration, the role of ecdysone signaling in producing the accelerated mitoses has not been investigated.…”