![Sample our Bioscience journals, sign in here to start your access, Latest two full volumes FREE to you for 14 days]({"type":"image" , "src" : "/sda/5925/TOC-Subject-Sample-2021-Bioscience.jpg"})
Abstract
The Drosophila lethal(2)denticleless (l(2)dtl) gene was originally reported as essential for embryogenesis and formation of the rows of tiny hairs on the larval ventral cuticle known as denticle belts. It is now well-established that l(2)dtl (also called cdt2) encodes a subunit of a Cullin 4-based E3 ubiquitin ligase complex that targets a number of key cell cycle regulatory proteins, including p21, Cdt1, E2F1 and Set8, to prevent replication defects and maintain cell cycle control. To investigate the role of l(2)dtl/cdt2 during development, we characterized existing l(2)dtl/cdt2 mutants and generated new deletion alleles, using P-element excision mutagenesis. Surprisingly, homozygous l(2)dtl/cdt2 mutant embryos developed beyond embryogenesis, had intact denticle belts, and lacked an observable embryonic replication defect. These mutants died during larval stages, affirming that loss of l(2)dtl/cdt2 function is lethal. Our data show that L(2)dtl/Cdt2 is maternally deposited, remains nuclear throughout the cell cycle, and has a previously unreported, elevated expression in the developing gonads. We also find that E2f1 regulates l(2)dtl/cdt2 expression during embryogenesis, possibly via several highly conserved putative E2f1 binding sites near the l(2)dtl/cdt2 promoter. Finally, hypomorphic allele combinations of the l(2)dtl/cdt2 gene result in a novel phenotype: viable, low-fertility males. We conclude that “denticleless” is a misnomer, but that l(2)dtl/cdt2 is an essential gene for Drosophila development.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Acknowledgments
The authors would like to thank the reviewers for valuable suggestions that strengthened the manuscript, Ursula Kurzik-Dumke for sending the l(2)dtl Ad-3 l(2)dtl Ag-4, l(2)dtl At, and l(2)dtl Ab-2 stocks, the Indiana University Bloomington Stock Center, Harvard Stock Center and Drosophila Genome Resource Center for Drosophila transposable element stocks and the l(2)dtl/cdt2 cDNA clone. We thank http://flybase.org for valuable database information; L.G. was supported by MBRS grant S06 GM 008049 (A.M. Abu-Shakra, PI). K.N.S. is supported by the S-STEM grant NSF-DUE 0807055 (PI: A. Tokuta). C.S. is supported by the Seeding Postdoctoral Innovators in Research and Education (SPIRE) program NIH-NIGMS grant #K12GM000678. This work funded by NIH: R01 GM57859 to R.J.D. and NIH-NIGMS SC2 GM083764 to S.C.S.K.