A Face-off Between Smaug and Caspar Modulates Primordial Germ Cell Count and Identity in Embryos

Overview

Journal Fly (Austin)

Specialty Biology

Date 2024 Dec 24

PMID 39718186

Authors

Girish Deshpande

Subhradip Das

Adheena Elsa Roy

Girish S Ratnaparkhi

Affiliations

Soon will be listed here.

Abstract

Proper formation and specification of Primordial Germ Cells (PGCs) is of special significance as they gradually transform into Germline Stem Cells (GSCs) that are ultimately responsible for generating the gametes. Intriguingly, not only the PGCs constitute the only immortal cell type but several specific determinants also underlying PGC specification such as Vasa, Nanos and Germ-cell-less are conserved through evolution. In , PGC formation and specification depends on two independent factors, the maternally deposited specialized cytoplasm (or germ plasm) enriched in germline determinants, and the mechanisms that execute the even partitioning of these determinants between the daughter cells. Prior work has shown that Oskar protein is necessary and sufficient to assemble the functional germ plasm, whereas centrosomes associated with the nuclei that invade the germ plasm are responsible for its equitable distribution. Our recent data suggests that Caspar, the orthologue of human Fas-associated factor-1 (FAF1) is a novel regulator that modulates both mechanisms that underlie the determination of PGC fate. Consistently, early blastoderm embryos derived from females compromised for display reduced levels of Oskar and defective centrosomes.

References

Jongens T, Ackerman L, Swedlow J, Jan L, Jan Y . Germ cell-less encodes a cell type-specific nuclear pore-associated protein and functions early in the germ-cell specification pathway of Drosophila. Genes Dev. 1994; 8(18):2123-36. DOI: 10.1101/gad.8.18.2123. View

Colonnetta M, Lym L, Wilkins L, Kappes G, Castro E, Ryder P . Antagonism between and Torso receptor regulates transcriptional quiescence underlying germline/soma distinction. Elife. 2021; 10. PMC: 7843132. DOI: 10.7554/eLife.54346. View

Fang J, Lerit D . Drosophila pericentrin-like protein promotes the formation of primordial germ cells. Genesis. 2019; 58(3-4):e23347. PMC: 8091889. DOI: 10.1002/dvg.23347. View

Lehmann R . Germ Plasm Biogenesis--An Oskar-Centric Perspective. Curr Top Dev Biol. 2016; 116:679-707. PMC: 4959550. DOI: 10.1016/bs.ctdb.2015.11.024. View

Jeske M, Moritz B, Anders A, Wahle E . Smaug assembles an ATP-dependent stable complex repressing nanos mRNA translation at multiple levels. EMBO J. 2010; 30(1):90-103. PMC: 3020108. DOI: 10.1038/emboj.2010.283. View

Tendulkar S, Hegde S, Garg L, Thulasidharan A, Kaduskar B, Ratnaparkhi A . Caspar, an adapter for VAPB and TER94, modulates the progression of ALS8 by regulating IMD/NFκB-mediated glial inflammation in a Drosophila model of human disease. Hum Mol Genet. 2022; 31(17):2857-2875. PMC: 9433731. DOI: 10.1093/hmg/ddac076. View

Cao W, Kabelitz S, Gupta M, Yeung E, Lin S, Rammelt C . Precise Temporal Regulation of Post-transcriptional Repressors Is Required for an Orderly Drosophila Maternal-to-Zygotic Transition. Cell Rep. 2020; 31(12):107783. PMC: 7372737. DOI: 10.1016/j.celrep.2020.107783. View

Ephrussi A, Lehmann R . Induction of germ cell formation by oskar. Nature. 1992; 358(6385):387-92. DOI: 10.1038/358387a0. View

Pae J, Cinalli R, Marzio A, Pagano M, Lehmann R . GCL and CUL3 Control the Switch between Cell Lineages by Mediating Localized Degradation of an RTK. Dev Cell. 2017; 42(2):130-142.e7. PMC: 5568677. DOI: 10.1016/j.devcel.2017.06.022. View

10.

Cline T, Meyer B . Vive la différence: males vs females in flies vs worms. Annu Rev Genet. 1996; 30:637-702. DOI: 10.1146/annurev.genet.30.1.637. View

11.

Colonnetta M, Schedl P, Deshpande G . Germline/soma distinction in embryos requires regulators of zygotic genome activation. Elife. 2023; 12. PMC: 9812407. DOI: 10.7554/eLife.78188. View

12.

Siddiqui N, Karaiskakis A, Goldman A, Eagle W, Low T, Luo H . Smaug regulates germ plasm assembly and primordial germ cell number in Drosophila embryos. Sci Adv. 2024; 10(15):eadg7894. PMC: 11014450. DOI: 10.1126/sciadv.adg7894. View

13.

Nakamura A, Sato K, Hanyu-Nakamura K . Drosophila cup is an eIF4E binding protein that associates with Bruno and regulates oskar mRNA translation in oogenesis. Dev Cell. 2004; 6(1):69-78. DOI: 10.1016/s1534-5807(03)00400-3. View

14.

Nelson M, Leidal A, Smibert C . Drosophila Cup is an eIF4E-binding protein that functions in Smaug-mediated translational repression. EMBO J. 2003; 23(1):150-9. PMC: 1271664. DOI: 10.1038/sj.emboj.7600026. View

15.

Doyle D, Burian F, Aharoni B, Klinder A, Menzel M, Nifras G . Germ Granule Evolution Provides Mechanistic Insight into Drosophila Germline Development. Mol Biol Evol. 2023; 40(8). PMC: 10414811. DOI: 10.1093/molbev/msad174. View

16.

Yohn C, Pusateri L, Barbosa V, Lehmann R . l(3)malignant brain tumor and three novel genes are required for Drosophila germ-cell formation. Genetics. 2004; 165(4):1889-900. PMC: 1462896. DOI: 10.1093/genetics/165.4.1889. View

17.

Das S, Hegde S, Wagh N, Sudhakaran J, Roy A, Deshpande G . Caspar specifies primordial germ cell count and identity in . Elife. 2024; 13. PMC: 11643641. DOI: 10.7554/eLife.98584. View

18.

Dahanukar A, Walker J, Wharton R . Smaug, a novel RNA-binding protein that operates a translational switch in Drosophila. Mol Cell. 1999; 4(2):209-18. DOI: 10.1016/s1097-2765(00)80368-8. View

19.

Kubikova J, Ubartaite G, Metz J, Jeske M . Structural basis for binding of Smaug to the GPCR Smoothened and to the germline inducer Oskar. Proc Natl Acad Sci U S A. 2023; 120(32):e2304385120. PMC: 10410706. DOI: 10.1073/pnas.2304385120. View

20.

Vastenhouw N, Cao W, Lipshitz H . The maternal-to-zygotic transition revisited. Development. 2019; 146(11). DOI: 10.1242/dev.161471. View