4.7 Article

Accelerated cell cycles enable organ regeneration under developmental time constraints in the Drosophila hindgut

Journal

DEVELOPMENTAL CELL
Volume 56, Issue 14, Pages 2059-+

Publisher

CELL PRESS
DOI: 10.1016/j.devcel.2021.04.029

Keywords

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Funding

  1. NIGMS [GM118447]

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The study reveals that the developing Drosophila hindgut can regenerate by accelerating the mitotic cell cycle, which is achieved through specific signaling pathways and must be completed within a certain timeframe.
Individual organ development must be temporally coordinated with development of the rest of the organism. As a result, cell division cycles in a developing organ occur on a relatively fixed timescale. 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 that the developing Drosophila hindgut regenerates by accelerating the mitotic cell cycle. This process is achieved by decreasing G1 length and requires the JAK/STAT ligand unpaired-3. Mitotic capacity is then terminated by the steroid hormone ecdysone receptor and the Sox transcription factor Dichaete. These two factors converge on regulation of a hindgut-specific enhancer of fizzy-related, a negative regulator of mitotic cyclins. Our findings reveal how the cell-cycle machinery and cytokine signaling can be adapted to accomplish developmental organ regeneration.

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