Tissue specific vulnerability to mitotic defects caused by mutations in the Drosophila ASPM homologue, Asp

Abstract

Misregulation of candidate stem cell marker ASPM, and its Drosophila homologue Asp, leads to either tumour formation or microcephaly, but the functional roles contributing to each are not understood. We reverse-engineered flies to express a version of Asp (AspLIE), predicted to have lost its ability to bind the phosphatase PP2A-B. Although AspLIE flies were viable, they exhibited splayed neural stem cell spindle poles under stress, and development was substantially delayed. A tissue-level analysis of microcephaly and midgut abnormalities in Asp mutants with a compromised spindle assembly checkpoint (SAC) demonstrates tissue-specific vulnerability to mitotic defects.