Control of endoreduplication domains in the Drosophila gut by the knirps and knirps-related genes.

ABSTRACT

Endoreduplication cycles that lead to an increase of DNA ploidy and cell size occur in distinct spatial and temporal patterns during Drosophila development. Only little is known about the regulation of these modified cell cycles. We have investigated fore- and hindgut development and we present evidence that the Drosophila knirps and knirps-related genes are key components to spatially restrict endoreduplication domains. Our lack and gain-of-function experiments show that knirps and knirps-related which encode nuclear orphan receptors transcriptionally repress S-phase genes of the cell cycle required for DNA replication and that this down-regulation is crucial for gut morphogenesis. Furthermore, we demonstrate that both genes are activated in overlapping expression domains in the fore- and hindgut in response to Wingless and Hedgehog activities emanating from epithelial signaling centers that control the regionalization of the gut tube. Our results provide a novel link between morphogen-dependent positional information and the spatio-temporal regulation of cell cycle activity in the gut.