Abstract
Gamete production in most animal species is initiated within an evolutionarily ancient multicellular germline structure, the germline cyst, whose interconnected premeiotic cells synchronously develop from a single progenitor arising just downstream from a stem cell. Cysts in mice, Drosophila, and many other animals protect developing sperm, while in females, cysts generate nurse cells that guard sister oocytes from transposons (TEs) and help them grow and build a Balbiani body. However, the origin and extreme evolutionary conservation of germline cysts remains a mystery. We suggest that cysts arose in ancestral animals like Hydra and Planaria whose multipotent somatic and germline stem cells (neoblasts) express genes conserved in all animal germ cells and frequently begin differentiation in cysts. A syncytial state is proposed to help multipotent stem cell chromatin transition to an epigenetic state with heterochromatic domains suitable for TE repression and specialized function. Most modern animals now lack neoblasts but have retained stem cells and cysts in their early germlines, which continue to function using this ancient epigenetic strategy.
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References
Alexandrova O, Schade M, Böttger A, David CN (2005) Oogenesis in Hydra: Nurse cells transfer cytoplasm directly to the growing oocyte. Dev Biol 281:91–101
Alié A, Leclère L, Jager M, Dayraud C, Chang P, Le Guyader H, Quéinnec E, Manuel M (2011) Somatic stem cells express Piwi and Vasa genes in an adult ctenophore: ancient association of “germline genes” with stemness. Dev Biol 350:183–197. https://doi.org/10.1016/j.ydbio.2010.10.019
Bentfeld ME (1971) Studies of oogenesis in the rotifer, Asplanchna. I. Fine structure of the female reproductive system. Z Zellforsch Mikrosk Anat 115(2):165–183. https://doi.org/10.1007/BF00391123
Bergero R, Ellis P, Haerty W, Larcombe L, Macaulay I, Mehta T, Mogensen M, Murray D, Nash W, Neale MJ, O’Connor R, Ottolini C, Peel N, Ramsey L, Skinner B, Suh A, Summers M, Sun Y, Tidy A, Rahbari R, Rathje C, Immler S (2021) Meiosis and beyond – understanding the mechanistic and evolutionary processes shaping the germline genome. Biol Rev Camb Philos Soc 96:822–841
Bosch TCG, David CN (1987) Stem cells of Hydra magnipapillata can differentiate into somatic cells and germ line cells. Dev Biol 21:182–191
Braun RE, Behringer RR, Peschon JJ, Brinster RL, Palmiter RD (1989) Genetically haploid spermatids are phenotypically diploid. Nature 337:373–376. https://doi.org/10.1038/337373a0
Brubacher JL, Huebner E (2011) Evolution and development of polarized germ cell cysts: new insights from a polychaete worm, Ophryotrocha labronica. Dev Biol 357(1):96–107. https://doi.org/10.1016/j.ydbio.2011.06.026. Epub 2011 Jun 25. PMID: 21726546
Büning J (1994) The insect ovary: ultrastructure, previtellogenic growth and evolution. Chapman and Hall, London
Büning J, Sohst S (1988) The flea ovary: ultrastructure and analysis of cell clusters. Tissue Cell 20:783–795. https://doi.org/10.1016/0040-8166(88)90023-7
Chen Z, Wang ZH, Zhang G, Bleck CKE, Chung DJ, Madison GP, Lindberg E, Combs C, Balaban RS, Xu H (2020) Mitochondrial DNA segregation and replication restrict the transmission of detrimental mutation. J Cell Biol 219:e201905160
Chen C, Liu W, Guo J, Liu Y, Liu X, Liu J, Dou X, Le R, Huang Y, Li C, Yang L, Kou X, Zhao Y, Wu Y, Chen J, Wang H, Shen B, Gao Y, Gao S (2021) Nuclear m6A reader YTHDC1 regulates the scaffold function of LINE1 RNA in mouse ESCs and early embryos. Protein Cell 12:455–474. https://doi.org/10.1007/s13238-021-00837-8
Chiappetta A, Liao J, Tian S, Trcek T (2022) Structural and functional organization of germ plasm condensates. Biochem J 479:2477–2495. https://doi.org/10.1042/BCJ20210815
Clough E, Tedeschi T, Hazelrigg T (2014) Epigenetic regulation of oogenesis and germ stem cell maintenance by the Drosophila histone methyltransferase Eggless/dSetDB1. Dev Biol 388:181–191. https://doi.org/10.1016/j.ydbio.2014.01.014
Cox RT, Spradling AC (2003) A Balbiani body and the fusome mediate mitochondrial inheritance during Drosophila oogenesis. Development 130:1579–1590. https://doi.org/10.1242/dev.00365
Czech B, Munafò M, Ciabrelli F, Eastwood EL, Fabry MH, Kneuss E, Hannon GJ (2018) piRNA-guided genome defense: from biogenesis to silencing. Annu Rev Genet 52:131–157. https://doi.org/10.1146/annurev-genet-120417-031441
David CN (2012) Interstitial stem cells in Hydra: multipotency and decision-making. Int J Dev Biol 56:489–497. https://doi.org/10.1387/ijdb.113476cd
de Cuevas M, Spradling AC (1998) Morphogenesis of the Drosophila fusome and its implications for oocyte specification. Development 125:2781–2789. https://doi.org/10.1242/dev.125.15.2781
de Cuevas M, Lee JK, Spradling AC (1996) alpha-spectrin is required for germline cell division and differentiation in the Drosophila ovary. Development 122:3959–3968. https://doi.org/10.1242/dev.122.12.3959
DeLuca SZ, Ghildiyal M, Pang LY, Spradling AC (2020) Differentiating Drosophila female germ cells initiate Polycomb silencing by regulating PRC2-interacting proteins. elife 9:e56922. https://doi.org/10.7554/eLife.56922
Denis H, Lacroix JC (1993) The dichotomy between germ line and somatic line, and the origin of cell mortality. Trends Genet 9:7–11. https://doi.org/10.1016/0168-9525(93)90065-P
Farnesi RM, Marinelli M, Tei S, Vagnetti D (1977) Ultrastructural research on the spermatogenesis in Dugesia lugubris. SL Riv Di Biol 70:113–136
Fawcett DW, Ito S, Slauterback D (1959) The occurrence of intercellular bridges in groups of cells exhibiting synchronous differentiation. J Biophys Biochem Cytol 5:453–460. https://doi.org/10.1083/jcb.5.3.453
Fell PE (1968) The involvement of nurse cells in oogenesis and embryonic development in the marine sponge, Haliclona ecbasis. J Morph 127:133–150
Fierro-Constaín L, Schenkelaars Q, Gazave E, Haguenauer A, Rocher C, Ereskovsky A, Borchiellini C, Renard E (2017) The conservation of the germline multipotency program, from sponges to vertebrates: a stepping stone to understanding the somatic and germline origins. Genome Biol Evol 9:474–488
Frydman HM, Spradling AC (2001) The receptor-like tyrosine phosphatase lar is required for epithelial planar polarity and for axis determination within drosophila ovarian follicles. Development 128:3209–3220. https://doi.org/10.1242/dev.128.16.3209
Ganot P, Bouquet JM, Kallesøe T, Thompson EM (2007) The Oikopleura coenocyst, a unique chordate germ cell permitting rapid, extensive modulation of oocyte production. Dev Biol 302(2):591–600. https://doi.org/10.1016/j.ydbio.2006.10.021
Gartner A, Boag PR, Blackwell TK (2008) Germline survival and apoptosis. WormBook Sep 4:1–20. https://doi.org/10.1895/wormbook.1.145.1
Gottanka J, Büning J (1990) Oocytes develop from interconnected cystocytes in the panoistic ovary of Nemoura sp. (Pictet) (Plecoptera: Nemouridae). Int J Insect Morphol Embryol 19:219–225
Gottanka J, Büning J (1993) Mayflies (Ephemeroptera), the most “primitive” winged insects, have telotrophic meroistic ovaries. Rouxs Arch Dev Biol 203:18–27
Hanna RE, Moffett D, Forster FI, Trudgett AG, Brennan GP, Fairweather I (2016) Fasciola hepatica: a light and electron microscope study of the ovary and of the development of oocytes within eggs in the uterus provides an insight into reproductive strategy. Vet Parasitol 221:93–103. https://doi.org/10.1016/j.vetpar.2016.03.011
Hill RS (1977) Studies on the ovotestis of the slug agriolimax reticulatus (Müller). 2. The epithelia. Cell Tissue Res 183(1):131–141. https://doi.org/10.1007/BF00219997
Hinnant TD, Merkle JA, Ables ET (2020) Coordinating proliferation, polarity, and cell fate in the Drosophila female germline. Front Cell Dev Biol 8:19
Issigonis M, Newmark PA (2019) From worm to germ: germ cell development and regeneration in planarians. Curr Top Dev Biol 135:127–153. https://doi.org/10.1016/bs.ctdb.2019.04.001
Issigonis M, Redkar AB, Rozario T, Khan UW, Mejia-Sanchez R, Lapan SW, Reddien PW, Newmark PA (2022) A Krüppel-like factor is required for development and regeneration of germline and yolk cells from somatic stem cells in planarians. PLoS Biol 20:e3001472. https://doi.org/10.1371/journal.pbio.3001472
Karpen GH, Spradling AC (1992) Analysis of subtelomeric heterochromatin in the Drosophila minichromosome Dp1187 by single P element insertional mutagenesis. Genetics 132:737–753. https://doi.org/10.1093/genetics/132.3.737
Khan UW, Newmark PA (2022) Somatic regulation of female germ cell regeneration and development in planarians. Cell Rep 38:110525. https://doi.org/10.1016/j.celrep.2022.110525
Kimoto C, Nakagawa H, Hasegawa R, Nodono H, Matsumoto M (2021) Co-localization of DrPiwi-1 and DrPiwi-2 in the oogonial cytoplasm is essential for oocyte differentiation in sexualized planarians. Cells Dev 167:203710. https://doi.org/10.1016/j.cdev.2021.203710
King RC (1970) Ovarian development in Drosophila melanogaster. Academic Press
Kloc M (2019) The Rove Beetle Creophilus maxillosus as a model system to study asymmetric division, oocyte specification, and the germ-somatic cell signaling. Results Probl Cell Differ 68:217–230. https://doi.org/10.1007/978-3-030-23459-1_9
Kloc M, Bilinski S, Dougherty MT, Brey EM, Etkin LD (2004) Formation, architecture and polarity of female germline cyst in Xenopus. Dev Biol 266(1):43–61. https://doi.org/10.1016/j.ydbio.2003.10.002. PMID: 14729477
Lavige JM, Lecher P (1982) Mttoses anormales dans les embryons a developpement bloque dans le systeme I-R de dysgenesie hybnde chez Drosophila melanogaster. Brol Cell 44:9–14
Lebo DPV, McCall K (2021) Murder on the ovarian express: a tale of non-autonomous cell death in the Drosophila ovary. Cell 10:1454–1473. https://doi.org/10.3390/cells10061454
Lei L, Spradling AC (2016) Mouse oocytes differentiate through organelle enrichment from sister cyst germ cells. Science 352:95–99
Lieber T, Jeedigunta SP, Palozzi JM, Lehmann R, Hurd TR (2019) Mitochondrial fragmentation drives selective removal of deleterious mtDNA in the germline. Nature 570:380–384
Lilly M, de Cuevas M, Spradling AC (2000) Cyclin A associates with the fusome during germline cyst formation in the Drosophila ovary. Dev Biol 218:53–63
Lim AK, Kai T (2007) Unique germ-line organelle, nuage, functions to repress selfish genetic elements in Drosophila melanogaster. Proc Natl Acad Sci 104(16):6714–6719. https://doi.org/10.1073/pnas.0701920104
Lim RS, Anand A, Nishimiya-Fujisawa C, Kobayashi S, Kai T (2014) Analysis of Hydra PIWI proteins and piRNAs uncover early evolutionary origins of the piRNA pathway. Dev Biol 386:237–251. https://doi.org/10.1016/j.ydbio.2013.12.007
Littlefield CL (1985) Germ cells in Hydra oligactis males. I. Isolation of a subpopulation of interstitial cells that is developmentally restricted to sperm production. Dev Biol 112:185–193
Littlefield CL (1991) Cell lineages in Hydra: isolation and characterization of an interstitial stem cell restricted to egg production in Hydra oligactis. Dev Biol 143:378–388
Liu Y, Kossack ME, McFaul ME, Christensen LN, Siebert S, Wyatt SR, Kamei CN, Horst S, Arroyo N, Drummond IA, Juliano CE, Draper BW (2022) Single-cell transcriptome reveals insights into the development and function of the zebrafish ovary. elife 11:e76014. https://doi.org/10.7554/eLife.76014
Lu K, Jensen L, Lei L, Yamashita YM (2017) Stay connected: a germ cell strategy. Trends Genet 33:971–978. https://doi.org/10.1016/j.tig.2017.09.001
Matova N, Cooley L (2001) Comparative aspects of animal oogenesis. Dev Biol 231:291–320
McCaig CM, Lin X, Farrell M, Rehain-Bell K, Shakes DC (2017) Germ cell cysts and simultaneous sperm and oocyte production in a hermaphroditic nematode. Dev Biol 430:362–373. https://doi.org/10.1016/j.ydbio.2017.08.010
Mercer M, Jang S, Ni C, Buszczak M (2021) The dynamic regulation of mRNA translation and ribosome biogenesis during germ cell development and reproductive aging. Front Cell Dev Biol 9:710186
Miller MA, Technau U, Smith KM, Steele RE (2000) Oocyte development in Hydra involves selection from competent precursor cells. Dev Biol 224:326–338
Munck A, David CN (1985) Cell proliferation and differentiation kinetics during spermatogenesis in Hydra carnea. Rouxs Arch Dev Biol 194:247–256
Mytlis A, Kumar V, Qiu T, Deis R, Hart N, Levy K, Masek M, Shawahny A, Ahmad A, Eitan H, Nather F, Adar-Levor S, Birnbaum RY, Elia N, Bachmann-Gagescu R, Roy S, Elkouby YM (2022) Control of meiotic chromosomal bouquet and germ cell morphogenesis by the zygotene cilium. Science 376:eabh3104. https://doi.org/10.1126/science.abh3104
Newmark PA, Sánchez AA (2022) Schmidtea happens: re-establishing the planarian as a model for studying the mechanisms of regeneration. Curr Top Dev Biol 147:307–344. https://doi.org/10.1016/bs.ctdb.2022.01.002
Ninova M, Chen YA, Godneeva B, Rogers AK, Luo Y, Fejes Tóth K, Aravin AA (2020) Su(var)2-10 and the SUMO pathway link piRNA-guided target recognition to chromatin silencing. Mol Cell 77:556–570. https://doi.org/10.1016/j.molcel.2019.11.012
Nishimiya-Fujisawa C, Kobayashi S (2012) Germline stem cells and sex determination in Hydra. Int J Dev Biol 56(6–8):499–508. https://doi.org/10.1387/ijdb.123509cf
Niu W, Spradling AC (2022) Mouse oocytes develop in cysts with the help of nurse cells. Cell 185:2576–2590
Ohlmeyer JT, Schüpbach T (2003) Encore facilitates SCF-Ubiquitin-proteasome-dependent proteolysis. Development 130:6339–6349
Onishi R, Yamanaka S, Siomi MC (2021) piRNA- and siRNA-mediated transcriptional repression in Drosophila, mice, and yeast: new insights and biodiversity. EMBO Rep 22:e53062. https://doi.org/10.15252/embr.202153062
Pang L-Y, DeLuca S, Zhu H, Urban JM, Spradling AC (2023) Chromatin and gene expression changes during female Drosophila germ cell development illuminate the biology of highly potent stem cells. elife, in press. See BioRxiv. https://doi.org/10.1101/2023.05.31.543160
Paré C, Suter B (2000) Subcellular localization of Bic-D::GFP is linked to an asymmetric oocyte nucleus. J Cell Sci 113(Pt 12):2119–2127. https://doi.org/10.1242/jcs.113.12.2119
Pepling ME, de Cuevas M, Spradling AC (1999) Germline cysts: a conserved phase of germ cell development? Trends Cell Biol 9:257–262
Percharde M, Lin CJ, Yin Y, Guan J, Peixoto GA, Bulut-Karslioglu A, Biechele S, Huang B, Shen X, Ramalho-Santos M (2018) A LINE1-nucleolin partnership regulates early development and ESC identity. Cell 174:391–405.e19. https://doi.org/10.1016/j.cell.2018.05.043
Praher D, Zimmermann B, Genikhovich G, Columbus-Shenkar Y, Modepalli V, Aharoni R, Moran Y, Technau U (2017) Characterization of the piRNA pathway during development of the sea anemone Nematostella vectensis. RNA Biol 14:1727–1741
Price, K, Dyuthi L, Tharakan M, Cooley L (2022) Evolutionarily conserved midbody reorganization precedes ring canal formation during gametogenesis. bioRxiv 2022.06.03.494691; https://doi.org/10.1101/2022.06.03.494691
Raiders SA, Eastwood MD, Bacher M, Priess JR (2017) Binucleate germ cells in Caenorhabditis elegans are removed by physiological apoptosis. PLoS Genet 14:e1007417. https://doi.org/10.1371/journal.pgen.1007417
Raz AA, Wurtzel O, Reddien PW (2021) Planarian stem cells specify fate yet retain potency during the cell cycle. Cell Stem Cell 28, 1307–1322.e5. https://doi.org/10.1016/j.stem.2021.03.021
Reddien PW (2018) The cellular and molecular basis for planarian regeneration. Cell 175:327–345
Reddien PW (2022) Positional information and stem cells combine to result in planarian regeneration. Cold Spring Harb Perspect Biol 14:a040717. https://doi.org/10.1101/cshperspect.a040717
Reddien PW, Oviedo NJ, Jennings JR, Jenkin JC, Sánchez Alvarado A (2005) SMEDWI-2 is a PIWI-like protein that regulates planarian stem cells. Science 310:1327–1330
Rozario T, Collins JJ 3rd, Newmark PA (2022) The good, the bad, and the ugly: from planarians to parasites. Curr Top Dev Biol 147:345–373. https://doi.org/10.1016/bs.ctdb.2021.12.015
Russell SL, Chappell L, Sullivan W (2019) A symbiont’s guide to the germline. Curr Top Dev Biol 135:315–351. https://doi.org/10.1016/bs.ctdb.2019.04.007
Samaddar M, Goudeau J, Sanchez M, Hall DH, Bohnert KA, Ingaramo M, Kenyon C (2021) A genetic screen identifies new steps in oocyte maturation that enhance proteostasis in the immortal germ lineage. elife 10:e62653. https://doi.org/10.7554/eLife.62653
Scherer G, Tschudi C, Perera J, Delius H, Pirrotta V (1982) B104, a new dispersed repeated gene family in Drosophila melanogaster and its analogies with retroviruses. J Mol Biol 157:435–451. https://doi.org/10.1016/0022-2836(82)90470-3
Schoenmakers HJ, Colenbrander PH, Peute J, van Oordt PG (1981) Anatomy of the ovaries of the starfish Asterias rubens (Echinodermata). A histological and ultrastructural study. Cell Tissue Res 217(3):577–597. https://doi.org/10.1007/BF00219366
Seah MKY, Wang Y, Goy PA, Loh HM, Peh WJ, Low DHP, Han BY, Wong E, Leong EL, Wolf G, Mzoughi S, Wollmann H, Macfarlan TS, Guccione E, Messerschmidt DM (2019) The KRAB-zinc-finger protein ZFP708 mediates epigenetic repression at RMER19B retrotransposons. Development 146:dev170266. https://doi.org/10.1242/dev.170266
Seidel HS, Smith TA, Evans JK, Stamper JQ, Mast TG, Kimble J (2018) C. elegans germ cells divide and differentiate in a folded tissue. Dev Biol 442:173–187
Seller CA, Cho CY, O’Farrell PH (2019) Rapid embryonic cell cycles defer the establishment of heterochromatin by Eggless/SetDB1 in Drosophila. Genes Dev 33:403–417. https://doi.org/10.1101/gad.321646.118
Seydoux G, Braun RE (2006) Pathway to totipotency: lessons from germ cells. Cell 127:891–904
Siebert S, Farrell JA, Cazet JF, Abeykoon Y, Primack AS, Schnitzler CE, Juliano CE (2019) Stem cell differentiation trajectories in Hydra resolved at single-cell resolution. Science 365:eaav9314. https://doi.org/10.1126/science.aav9314
Spradling AC, de Cuevas M, Drummond-Barbosa D, Keyes L, Lilly M, Pepling M, Xie T (1997) The Drosophila germarium: stem cells, germ line cysts, and oocytes. Cold Spring Harb Symp Quant Biol 62:25–34
Spradling AC, Niu W, Yin Q, Pathak M, Maurya B (2022) Conservation of oocyte development in germline cysts from Drosophila to mouse. elife 11:e83230. https://doi.org/10.7554/eLife.83230. PMC9708067
Strome S, Lehmann R (2007) Germ versus soma decisions: lessons from flies and worms. Science 316:392–393
Świątek P, Urbisz AZ (2019) Architecture and life history of female germ-line cysts in clitellate annelids. Results Probl Cell Differ 68:515–551
Technau U, Miller MA, Bridge D, Steele RE (2003) Arrested apoptosis of nurse cells during Hydra oogenesis and embryogenesis. Dev Biol 260:191–206. https://doi.org/10.1016/s0012-1606(03)00241-0. PMID: 12885564
Teefy BB, Siebert S, Cazet JF, Lin H, Juliano CE (2020) PIWI–piRNA pathway-mediated transposable element repression in Hydra somatic stem cells. RNA 26:550–563
Telfer WH (1975) Development and physiology of the oocyte-nurse cell syncytium. Adv Insect Physiol 11:223–319
Tworzydlo W, Kisiel E, Jankowska W, Bilinski SM (2014) Morphology and ultrastructure of the germarium in panoistic ovarioles of a basal “apterygotous” insect, Thermobia domestica. Zoology (Jena) 117:200–206
Woodland HR (2016) The birth of animal development: multicellularity and the germline. Curr Top Dev Biol 117:609–630. https://doi.org/10.1016/bs.ctdb.2015.10.020
Zeng A, Li H, Guo L, Gao X, McKinney S, Wang Y, Yu Z, Park J, Semerad C, Ross E, Cheng LC, Davies E, Lei K, Wang W, Perera A, Hall K, Peak A, Box A, Sánchez-Alvarado A (2018) Prospectively isolated tetraspanin+ neoblasts are adult pluripotent stem cells underlying planaria regeneration. Cell 173:1593–1608.e20. https://doi.org/10.1016/j.cell.2018.05.006
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Spradling, A.C. (2024). The Ancient Origin and Function of Germline Cysts. In: Kloc, M., Uosef, A. (eds) Syncytia: Origin, Structure, and Functions. Results and Problems in Cell Differentiation, vol 71. Springer, Cham. https://doi.org/10.1007/978-3-031-37936-9_1
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