Maternally Inherited Intron Coordinates Primordial Germ Cell Homeostasis During Drosophila Embryogenesis

Overview

Journal Cell Death Differ

Specialty Cell Biology

Date 2020 Oct 23

PMID 33093656

Citations 3

Authors

Ismail Osman

Jun Wei Pek

Affiliations

Soon will be listed here.

Abstract

Primordial germ cells (PGCs) give rise to the germline stem cells (GSCs) in the adult Drosophila gonads. Both PGCs and GSCs need to be tightly regulated to safeguard the survival of the entire species. During larval development, a non-cell autonomous homeostatic mechanism is in place to maintain PGC number in the gonads. Whether such germline homeostasis occurs during early embryogenesis before PGCs reach the gonads remains unclear. We have previously shown that the maternally deposited sisRNA sisR-2 can influence GSC number in the female progeny. Here we uncover the presence of a homeostatic mechanism regulating PGCs during embryogenesis. sisR-2 represses PGC number by promoting PGC death. Surprisingly, increasing maternal sisR-2 leads to an increase in PGC death, but no drop in PGC number was observed. This is due to ectopic division of PGCs via the de-repression of Cyclin B, which is governed by a genetic pathway involving sisR-2, bantam and brat. We propose a cell autonomous model whereby germline homeostasis is achieved by preserving PGC number during embryogenesis.

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References

Mahowald A . Assembly of the Drosophila germ plasm. Int Rev Cytol. 2000; 203:187-213. DOI: 10.1016/s0074-7696(01)03007-8. View

Su T, Campbell S, Ofarrell P . The cell cycle program in germ cells of the Drosophila embryo. Dev Biol. 1998; 196(2):160-70. DOI: 10.1006/dbio.1998.8855. View

Richardson B, Lehmann R . Mechanisms guiding primordial germ cell migration: strategies from different organisms. Nat Rev Mol Cell Biol. 2009; 11(1):37-49. PMC: 4521894. DOI: 10.1038/nrm2815. View

Yamada Y, Davis K, Coffman C . Programmed cell death of primordial germ cells in Drosophila is regulated by p53 and the Outsiders monocarboxylate transporter. Development. 2007; 135(2):207-16. DOI: 10.1242/dev.010389. View

Slaidina M, Lehmann R . Quantitative Differences in a Single Maternal Factor Determine Survival Probabilities among Drosophila Germ Cells. Curr Biol. 2017; 27(2):291-297. PMC: 5263097. DOI: 10.1016/j.cub.2016.11.048. View

Sato K, Hayashi Y, Ninomiya Y, Shigenobu S, Arita K, Mukai M . Maternal Nanos represses hid/skl-dependent apoptosis to maintain the germ line in Drosophila embryos. Proc Natl Acad Sci U S A. 2007; 104(18):7455-60. PMC: 1854842. DOI: 10.1073/pnas.0610052104. View

Sano H, Renault A, Lehmann R . Control of lateral migration and germ cell elimination by the Drosophila melanogaster lipid phosphate phosphatases Wunen and Wunen 2. J Cell Biol. 2005; 171(4):675-83. PMC: 2171572. DOI: 10.1083/jcb.200506038. View

Gilboa L, Lehmann R . Soma-germline interactions coordinate homeostasis and growth in the Drosophila gonad. Nature. 2006; 443(7107):97-100. DOI: 10.1038/nature05068. View

Osman I, Tay M, Pek J . Stable intronic sequence RNAs (sisRNAs): a new layer of gene regulation. Cell Mol Life Sci. 2016; 73(18):3507-19. PMC: 11108444. DOI: 10.1007/s00018-016-2256-4. View

10.

Chan S, Pek J . Stable Intronic Sequence RNAs (sisRNAs): An Expanding Universe. Trends Biochem Sci. 2018; 44(3):258-272. DOI: 10.1016/j.tibs.2018.09.016. View

11.

Tay M, Pek J . Maternally Inherited Stable Intronic Sequence RNA Triggers a Self-Reinforcing Feedback Loop during Development. Curr Biol. 2017; 27(7):1062-1067. DOI: 10.1016/j.cub.2017.02.040. View

12.

Wong J, Akhbar F, Ng A, Tay M, Loi G, Pek J . DIP1 modulates stem cell homeostasis in Drosophila through regulation of sisR-1. Nat Commun. 2017; 8(1):759. PMC: 5624886. DOI: 10.1038/s41467-017-00684-4. View

13.

Pek J, Osman I, Tay M, Zheng R . Stable intronic sequence RNAs have possible regulatory roles in Drosophila melanogaster. J Cell Biol. 2015; 211(2):243-51. PMC: 4621838. DOI: 10.1083/jcb.201507065. View

14.

Petrella L, Smith-Leiker T, Cooley L . The Ovhts polyprotein is cleaved to produce fusome and ring canal proteins required for Drosophila oogenesis. Development. 2007; 134(4):703-12. DOI: 10.1242/dev.02766. View

15.

Van Doren M, Williamson A, Lehmann R . Regulation of zygotic gene expression in Drosophila primordial germ cells. Curr Biol. 1998; 8(4):243-6. DOI: 10.1016/s0960-9822(98)70091-0. View

16.

Tracey Jr W, Ning X, Klingler M, Kramer S, Gergen J . Quantitative analysis of gene function in the Drosophila embryo. Genetics. 2000; 154(1):273-84. PMC: 1460918. DOI: 10.1093/genetics/154.1.273. View

17.

Brennecke J, Hipfner D, Stark A, Russell R, Cohen S . bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell. 2003; 113(1):25-36. DOI: 10.1016/s0092-8674(03)00231-9. View

18.

Herranz H, Hong X, Cohen S . Mutual repression by bantam miRNA and Capicua links the EGFR/MAPK and Hippo pathways in growth control. Curr Biol. 2012; 22(8):651-7. DOI: 10.1016/j.cub.2012.02.050. View

19.

Harris R, Pargett M, Sutcliffe C, Umulis D, Ashe H . Brat promotes stem cell differentiation via control of a bistable switch that restricts BMP signaling. Dev Cell. 2011; 20(1):72-83. PMC: 3178012. DOI: 10.1016/j.devcel.2010.11.019. View

20.

Patil V, Kai T . Repression of retroelements in Drosophila germline via piRNA pathway by the Tudor domain protein Tejas. Curr Biol. 2010; 20(8):724-30. DOI: 10.1016/j.cub.2010.02.046. View