Abstract
ABSTRACTStem cells continuously generate differentiating daughter cells and are essential for tissue homeostasis and development. Their capacity to self-renew as undifferentiated and actively dividing cells is controlled by either external signals from a cellular environment, the stem cell niche, or asymmetric distribution of cell fate determinants during cell division. Here we report that the protein kinase Bällchen (BALL) is required to prevent differentiation as well as to maintain normal proliferation of neuronal stem cells of Drosophila melanogaster, called neuroblasts. Our results show that the brains of ball mutant larvae are severely reduced in size, which is caused by a reduced proliferation rate of the neuroblasts. Moreover, ball mutant neuroblasts gradually lose the expression of the neuroblast determinants Miranda and aPKC, suggesting their premature differentiation. Our results indicate that BALL represents a novel cell intrinsic factor with a dual function regulating the proliferative capacity and the differentiation status of neuronal stem cells during development.
Highlights
Multicellular organisms have to maintain a balance between cell proliferation and differentiation
We have recently found that germline stem cells (GSCs) self-renewal requires the activity of the gene ballchen (Herzig et al, 2014), which encodes a member of the metazoan specific VRK-1 protein kinase family (Aihara et al, 2004). ball orthologous from vertebrates and invertebrates encode proteins that phosphorylate the Barrier-to-Autointegration Factor protein (BAF), which is proposed to participate in the establishment of higher order chromatin structures (Gorjanacz et al, 2007; Nichols et al, 2006; Bengtsson and Wilson, 2006; Lancaster et al, 2007)
We found that ball2 mutant postembryonic neuroblasts (pNBs) were still dividing at 96 h after larval hatching (ALH), but the number of mitotic pNBs was significantly lower than the number of mitotic control pNBs (Fig. 3F)
Summary
Multicellular organisms have to maintain a balance between cell proliferation and differentiation. Self-renewed NBs inherit the apical cortical proteins such as the atypical protein kinase C, Par, Bazooka/Par, Inscuteable, Partner of Inscuteable and GaI, whereas the basal cortical proteins, that include cell fate determinants such as Prospero and Brat, are inherited by the differentiating ganglion mother cell (GMC). Their localized retention requires the coiled-coil adaptor protein Miranda (MIRA), which is subsequently degraded in the differentiating GMC (Shen et al, 1997). Our results on neuronal stem cells indicate that distinct stem cell populations employ a common factor, BALL, to remain undifferentiated
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
