Alstrom syndrome gene is a stem-cell-specific regulator of centriole duplication in the Drosophila testis.

Cuie Chen,Yukiko M Yamashita

doi:10.7554/elife.59368

Abstract

Asymmetrically dividing stem cells often show asymmetric behavior of the mother versus daughter centrosomes, whereby the self-renewing stem cell selectively inherits the mother or daughter centrosome. Although the asymmetric centrosome behavior is widely conserved, its biological significance remains largely unclear. Here, we show that Alms1a, a Drosophila homolog of the human ciliopathy gene Alstrom syndrome, is enriched on the mother centrosome in Drosophila male germline stem cells (GSCs). Depletion of alms1a in GSCs, but not in differentiating germ cells, results in rapid loss of centrosomes due to a failure in daughter centriole duplication, suggesting that Alms1a has a stem-cell-specific function in centrosome duplication. Alms1a interacts with Sak/Plk4, a critical regulator of centriole duplication, more strongly at the GSC mother centrosome, further supporting Alms1a's unique role in GSCs. Our results begin to reveal the unique regulation of stem cell centrosomes that may contribute to asymmetric stem cell divisions.

Highlights

Many stem cells divide asymmetrically to generate daughter cells with distinct fates: one self-renewing stem cell and one differentiating cell
Why is Alms1a’s function to promote centriole duplication together with Sak only required in germline stem cells (GSCs) but not in SGs? Interestingly, we found that RNAi-mediated knockdown of alms1a in GSCs resulted in the excessive enrichment of both Sak and Sas-6 at the elongated mother centriole that remains after all other centrosomes are depleted (Figure 6F–K)
We identified a centrosomal protein Alms1a, a homolog of a causative gene of human ciliopathy Alstrom syndrome, that exhibits asymmetric localization between mother and daughter centrosomes in Drosophila male GSCs

Summary

Introduction

Many stem cells divide asymmetrically to generate daughter cells with distinct fates: one self-renewing stem cell and one differentiating cell. Dividing stem cells in several systems show stereotypical inheritance of the mother vs daughter centrosomes, where the mother or daughter centrosome is consistently inherited by stem cells (Conduit and Raff, 2010; Habib et al, 2013; Januschke et al, 2011; Wang et al, 2009; Yamashita et al, 2007). This observation has provoked the idea that centrosome asymmetry in stem cells might play a critical role during asymmetric cell divisions and that stem cell centrosomes might be uniquely regulated. The abnormally elongated mother centrosome in klp10A-depleted GSCs result in mitotic spindles with

Objectives

Results

Conclusion