The Drosophila Nuclear Lamina Protein Otefin Is Required for Germline Stem Cell Survival

•Germaria in young ote mutant ovaries display GSC loss and expanded GSC numbers•A primary defect in ote−/− germ cells is a block in differentiation•Transcription of the bam differentiation gene is not activated in ote−/− GSCs•Age-dependent ote−/− GSC loss results from cell death, not differentiation

SummaryLEM domain (LEM-D) proteins are components of an extensive protein network that assembles beneath the inner nuclear envelope. Defects in LEM-D proteins cause tissue-restricted human diseases associated with altered stem cell homeostasis. Otefin (Ote) is a Drosophila LEM-D protein that is intrinsically required for female germline stem cell (GSC) maintenance. Previous studies linked Ote loss with transcriptional activation of the key differentiation gene bag-of-marbles (bam), leading to the model in which Ote tethers the bam gene to the nuclear periphery for gene silencing. Using genetic and phenotypic analyses of multiple ote−/− backgrounds, we obtained evidence that is inconsistent with this model. We show that bam repression is maintained in ote−/− GSCs and that germ cell loss persists in ote−/−, bam−/− mutants, together demonstrating that GSC loss is independent of bam transcription. We show that the primary defect in ote−/− GSCs is a block of differentiation, which ultimately leads to germ cell death.