Regulation of intestinal stem cell activity by a mitotic cell cycle regulator Polo in Drosophila

Abstract

Maintaining a definite and stable pool of dividing stem cells plays an important role in organ development. This process requires an appropriate progression of mitosis for proper spindle orientation and polarity to ensure the ability of stem cells to proliferate and differentiate correctly. Polo-like kinases (Plks)/Polo are the highly conserved serine/threonine kinases involved in the initiation of mitosis as well as in the progression of the cell cycle. Although numerous studies have investigated the mitotic defects upon loss of Plks/Polo in cells, little is known about the in vivo consequences of stem cells with abnormal Polo activity in the context of tissue and organism development. The current study aimed to investigate this question using the Drosophila intestine, an organ dynamically maintained by the intestinal stem cells (ISCs). The results indicated that the polo depletion caused a reduction in the gut size due to a gradual decrease in the number of functional ISCs. Interestingly, the polo-deficient ISCs showed an extended G2/M phase and aneuploidy and were subsequently eliminated by premature differentiation into enterocytes (ECs). In contrast, the constitutively active Polo (poloT182D) suppressed ISC proliferation, induced abnormal accumulation of β-tubulin in cells, and drove ISC loss via apoptosis. Therefore, Polo activity should be properly maintained for optimal stem cell function. Further analysis suggested that polo was a direct target gene of Sox21a, a Sox transcription factor that critically regulates stem cell activity. Together, this study provided a novel perspective on the correlation between the progression of mitosis and the ISC function in Drosophila.

Testis- and ovary-expressedpolotranscripts and gene duplications affect male fertility when expressed in the germline

“…In this hypothesis, ectopic expression of Dpse-polo-dup1 would be less costly than expression of the fully functional Plks encoded by polo and Dpse-polo. Negative effects of high polo expression have been shown in D. melanogaster intestinal stem cells, where constitutively active Polo suppresses intestinal stem cell proliferation, induces abnormal accumulation of β-tubulin in cells, and drives stem cell loss via apoptosis (Zhang et al 2023). However, other experiments have shown Polo overexpression by 2.5-fold using GAL4>UAS does not affect its physiological function in mitosis (Martins et al 2009).…”