Discovery of Alstrom syndrome gene as a regulator of centrosome duplication in asymmetrically dividing stem cells in Drosophila.

Abstract

Stereotypical inheritance of the mother vs. daughter centrosomes has been reported in several stem cells that divide asymmetrically. We report the identification of a protein that exhibits asymmetric localization between mother and daughter centrosomes in asymmetrically dividing Drosophila male germline stem cells (GSCs). We show that Alms1a, a Drosophila homolog of the causative gene for the human ciliopathy Alstrom Syndrome, is a ubiquitous mother centriole protein with a unique additional localization to the daughter centriole only in the mother centrosome of GSCs. Depletion of alms1a results in rapid loss of centrosomes due to failure in daughter centriole duplication. We reveal that alms1a is specifically required for centriole duplication in asymmetrically dividing cells but not in symmetrically dividing differentiating cells in multiple stem cell lineages. The unique requirement of alms1a in asymmetric dividing cells may shed light onto the molecular mechanisms of Alstrom syndrome pathogenesis.