Emerin preserves stem cell survival through maintenance of centrosome and nuclear lamina structure

Development. 2024 Nov 15;151(22):dev204219. doi: 10.1242/dev.204219. Epub 2024 Nov 13.

Abstract

Drosophila female germline stem cells (GSCs) complete asymmetric mitosis in the presence of an intact, but permeable, nuclear envelope and nuclear lamina (NL). This asymmetric division requires a modified centrosome cycle, wherein mitotic centrosomes with mature pericentriolar material (PCM) embed in the NL and interphase centrosomes with reduced PCM leave the NL. This centrosome cycle requires Emerin, an NL protein required for GSC survival and germ cell differentiation. In emerin mutants, interphase GSC centrosomes retain excess PCM, remain embedded in the NL and nucleate microtubule asters at positions of NL distortion. Here, we investigate the contributions of abnormal interphase centrosomes to GSC loss. Remarkably, reducing interphase PCM in emerin mutants rescues GSC survival and partially restores germ cell differentiation. Direct tests of the effects of abnormal centrosomes were achieved by expression of constitutively active Polo kinase to drive enlargement of interphase centrosomes in wild-type GSCs. Notably, these conditions failed to alter NL structure or decrease GSC survival. However, coupling enlarged interphase centrosomes with nuclear distortion promoted GSC loss. These studies establish that Emerin maintains centrosome structure to preserve stem cell survival.

Keywords: Asymmetric division; Centrosome; LEM domain; Lamin; Nuclear structure; Otefin; Polo.

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Survival*
  • Centrosome* / metabolism
  • Drosophila Proteins* / genetics
  • Drosophila Proteins* / metabolism
  • Drosophila melanogaster / metabolism
  • Female
  • Germ Cells / cytology
  • Germ Cells / metabolism
  • Interphase
  • Membrane Proteins* / genetics
  • Membrane Proteins* / metabolism
  • Mitosis
  • Mutation / genetics
  • Nuclear Lamina* / metabolism
  • Nuclear Proteins* / genetics
  • Nuclear Proteins* / metabolism
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Stem Cells* / cytology
  • Stem Cells* / metabolism

Substances

  • Nuclear Proteins
  • emerin
  • Drosophila Proteins
  • Membrane Proteins
  • Protein Serine-Threonine Kinases
  • polo protein, Drosophila