secrets of the deep · follicles must be being made somewhere in young mouse ovaries. they proposed...
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follicles must be being made somewhere inyoung mouse ovaries. They proposed anactive population of germline stem cells asthe most likely source.
Four lines of evidence from the newstudy4 strongly corroborate the existence ofgermline stem cells and the resultant on-going follicle production in the ovaries ofpostnatal mice. First, Johnson et al. found apopulation of 63�8 germ cells near the sur-face of the ovary that were outside folliclesand that had the general characteristics ofgermline stem cells. They expressed a con-served germ-cell marker known as Vasa andwere actively cycling — that is, they pro-duced new cells.
Second, the authors found germ cells thathad not yet developed into follicles in theovary. This would be expected if the progenyof the germline stem cells were developinginto new oocytes; indeed, Johnson et al.4
identified germ cells that expressed severalmarkers of this process. The overall levels of these marker proteins in the ovariesamounted to 6–25% of the levels that occurin adult testes, which contain large numbersof cycling germline stem cells and theirmaturing progeny (which express these same proteins).
Third, that the progeny of germ cells wenton to produce follicles was shown by graftinga small part of a fluorescently labelled ovaryinto an unmarked host ovary. Follicles thatcomprised fluorescently labelled oocytessurrounded by unmarked follicle cells couldsubsequently be found. Germ cells hadtherefore moved out of the graft and formeda follicle within the host ovary, somethingthat would be expected only if follicle forma-tion was ongoing.
Last, treating mice with the toxic drugbusulfan, which selectively kills malegermline stem cells, rapidly depleted thepool of young follicles. The rapid time framein which it did so suggested that femalegermline stem cells in mice contribute anaverage of 77 new follicles per ovary per day. The group’s findings4 all point to theexistence of germline stem cells and arequirement for them in maintaining folliclenumbers throughout the reproductive life-time of female mice.
The finding raises many interesting andimportant questions. Determining the exactnumber and location of these functionalgermline stem cells will require tagging germ cells and showing that their descen-dants form follicles and, ultimately, matureoocytes. Such lineage-tracing experimentswill also address whether the progeny ofmouse germline stem cells differentiatedirectly into oocytes or whether they firstincrease their numbers by forming inter-connected ‘germ-cell cysts’. These structuresare present during fetal stages5 and form after germline stem-cell division in mostorganisms.
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Another issue will be to assess the relativeuse of follicles generated during fetal lifecompared with those produced by adultstem cells. Do the follicles produced beforebirth fail to survive to reproductive maturity,so that female fertility actually depends onthe presence of young follicles producedrecently from germline stem cells? And doesthe loss of these stem cells soon lead to follicleageing,depletion and reproductive decline?
Now that germline stem cells in themouse have been discovered, determiningthe cellular and molecular mechanisms thatmaintain them as such will be the mission ofmany a scientist.Previous work on Drosophilagermline stem cells might usefully guide this quest. These stem cells reside in a nichewhere certain conditions are met to ensurethat they continue to survive and function.
Germline stem cells have several require-ments: contact with a specific body (non-gamete) cell type; a particular signal, a member of the ‘bone morphogenetic pro-tein’ family; and the expression of a smallnumber of special regulatory genes1,6. Manyof these mechanisms have probably beenconserved between species. All these issuescan now be addressed in mice by using exist-ing technology.
Last, but far from least, the question oneveryone’s lips will be whether there aregermline stem cells in the human ovary.Germline stem cells in humans might easilyhave been missed for the same reasons thatthey escaped detection in mice for so long.Indeed, the work of Johnson et al.4 raises thestrong possibility that the reproductivedecline seen in female thirtysomethings isdue to the depletion of germline stem cellscoupled with a high follicular age-dependentincidence of defects occurring during reduc-tive divisions when oocytes mature7. ■
Allan C. Spradling is in the Howard HughesMedical Institute Laboratory, Carnegie Institution of Washington, 115 West University Parkway, Baltimore,Maryland 21210, USA.e-mail: [email protected]
1. Spradling, A., Drummond-Barbosa, D. & Kai, T. Nature 414,
12–18 (2001).
2. Raven, C. P. Oogenesis: The Storage of Developmental
Information (Pergamon, New York, 1961).
3. Tilly, J. L. Nature Rev. Mol. Cell Biol. 2, 838–848 (2001).
4. Johnson, J., Canning, J., Kaneko, T., Pru, J. K. & Tilly, J. L.
Nature 428, 145–150 (2004).
5. Pepling, M. E. & Spradling, A. C. Development 125,
3323–3328 (1998).
6. Song, X., Zhu, C. H., Doan, C. & Xie, T. Science 296,
1855–1857 (2002).
7. Pellestor, F., Andréo, B., Arnal, F., Humeau, C. & Demaille, J.
Hum. Genet. 112, 195–203 (2003).
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Figure 1 Falling fertility. The graph shows the decreasing success rates (live births) with increasing age for in vitro fertilizationusing embryos derived from a woman’s own eggs compared with using eggs from ayoung donor.
Planetary science
Secrets of the deepJonathan Aurnou
The magnetic fields of Uranus and Neptune are markedly different fromthose of other planets in the Solar System. Can this be attributed tostructural differences deep inside the planets?
Several planets in the Solar System —including Jupiter and its moonGanymede, Saturn and possibly
Mercury1 — have a magnetic field that issimilar to Earth’s. The magnetic fieldsresemble that of a bar magnet,with the align-ment of north and south poles oriented close to the rotation axis of the planet. Butdata from NASA’s Voyager 2 probe haveshown that the magnetic fields of Uranusand Neptune are different from those ofother planets. Their fields are effectivelytipped over: instead of aligning along therotational axis, the north–south axis of thefield lies midway or closer to the equatorial
plane. These unusual magnetic fields havebeen difficult to model. But on page 151 ofthis issue, Stanley and Bloxham’s simula-tions2 show that, by altering the descriptionof the internal structure of the planets,complex magnetic fields can be generatedthat are similar in structure to those ofUranus and Neptune.
All models of the generation of planetarymagnetic fields include the same essentialingredients. There must be a region of elec-trically conducting fluid and an energysource to drive the motion of that fluid. Amodel of Earth’s field, for instance, simu-lates its iron-rich molten outer core (the
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conducting fluid) as well as the planetarycooling (or radioactive heating) that drivesconvective currents in the planet’s interior.Another necessary element is the planetaryrotation that organizes the fluid motions:well-organized fluid motions can generate alarge-scale magnetic field, but disorganizedfluid motions produce fields that tend, onaverage, to cancel out. Only when all theseconditions are met, in a model or a planet,is it possible for the moving fluid to create a dynamo that generates a planetary mag-netic field3.
For Earth-like planets, convectivemotions are typically modelled in a thickrotating shell of electrically conductingfluid. That shell surrounds a relatively small,electrically conducting, solid inner core (Fig. 1a). The result is a dipolar, bar-magnetstyle magnetic field that is almost alignedwith the rotation axis. A similar set-up holdsfor the gas giants Jupiter and Saturn (Fig.1b):a very small rocky core is surrounded by athick layer of convecting metallic hydrogen.(Hydrogen under very high pressure dissoci-ates into free-moving protons and electrons,and is hence called ‘metallic’.)
But such models are largely unable tocapture the complexities of the magneticfields of Uranus and Neptune. The measure-ments made by Voyager 2 around these planets revealed that their fields are not predominantly dipolar (like a bar magnet),
but also have a quadrupole component (as though produced by a combination oftwo bar magnets, with two north and twosouth poles). In addition, the main axis oftheir fields lies far from the rotation axis.On Uranus, the main magnetic-field axis istipped over from the rotation axis by about59� in latitude; on Neptune, the main axis istipped over by about 47�.
Stanley and Bloxham2 have constructed amodel that simulates these characteristic differences. Instead of a thick convectingshell and a solid inner region, they considerUranus and Neptune to have a comparativelythin outermost region of convecting ionizedfluid surrounding a non-convecting ionizedinner-fluid ‘ocean’. This modified structurefollows the suggestion of earlier work4,5,based on anomalously low planetary heat-flow measurements, that deep convectivefluid motions on Uranus and Neptune mightbe occurring in only a relatively thin shell ofthe planetary interior (Fig.1c).
Stanley and Bloxham’s model generatesfields similar to those observed on Uranusand Neptune.Indeed,it seems that a relativelysimple alteration in the structure of the con-vecting region can lead to a fundamentalchange in the type of magnetic field that adynamo model produces. Why this funda-mental change in magnetic-field structureshould occur remains unclear. Stanley andBloxham propose that the less constraining
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effects of the fluid inner region allow morecomplex magnetic-field morphologies todevelop. However, this argument does notexplain how the complex magnetic fields areproduced and maintained.
It also remains to be seen how robust thiscomplex field behaviour is.Stanley and Blox-ham present a single-case result in theirstudy. Are complex fields produced in allcases with this internal structure, or only,for instance, in those that have convectivemotions of a particular strength? Thesequestions aside, their model clearly andimpressively demonstrates that the samefundamental process — convection in arotating spherical shell of electrically con-ducting fluid — can explain the basic struc-ture of all the dynamo-generated planetarymagnetic fields presently observed in theSolar System. ■
Jonathan Aurnou is in the Department of Earth andSpace Science, University of California, Los Angeles,595 Charles Young Drive East, Los Angeles,California 90095-1567, USA.e-mail: [email protected]. Solomon, S. C. et al. Planet. Space. Sci. 49, 1445–1465
(2001).
2. Stanley, S. & Bloxham, J. Nature 428, 151–153 (2004).
3. Busse, F. H. Phys. Fluids 14, 1301–1314 (2002).
4. Podolak, M., Hubbard, W. B. & Stevenson, D. J. in Uranus
(eds Bergstrahl, J. T., Miner, E. D. & Matthews, M. S.) 29–61
(Univ. Arizona Press, 1991).
5. Hubbard, W. B., Podolak, M. & Stevenson, D. J. in Neptune and
Triton (ed. Cruikshank, D. P.) 109–138 (Univ. Arizona Press,
1995).
Figure 1 Magnetic fields and interior structures of the planets. a, Earth has a predominantly dipolar magnetic field, like that of a bar magnet.Magnetic north and the North Pole do not quite coincide: the magneticaxis is tilted by 11� relative to the axis of rotation of the planet. The field is generated by the dynamo action of convective currents in the moltenouter core, around a solid conducting inner core. b, The gas giant Jupiter also has a strongly dipolar field, whose axis is aligned at 10� to the planet’s rotational axis. In Jupiter’s interior, convection occurs in athick shell of metallic (dissociated) hydrogen that surrounds the
planet’s small, rocky core. c, Uranus, in contrast, has comparablequadrupole and dipole components in its magnetic field. Strikingly,the magnetic-field axis is oriented at 59� to the planet’s axis of rotation.Using a revised description of the planet’s interior — with a much thinner convecting shell around a non-convecting but fluid inner region — Stanley and Bloxham2 have devised a dynamo model thatgenerates a magnetic field that is similar in structure to Uranus’(and Neptune’s) anomalous field. (Rotation axes are artificially alignedvertically for ease of comparison.)
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