Gene implicated in germ-cell development

Summaries of newsworthy papers include Disrupting viruses, microRNA implicated in cell fate decisions, Methane bubbling up, Action representation in the autistic brain, A common susceptibility locus for several types of cancer, Getting to the root of oculo-facial-cardio-dental syndrome, A tale of two spores and Specialized skin helpers


For papers that will be published online on 05 July 2009

This press release is copyrighted to the Nature journals mentioned below.

This press release contains:

· Summaries of newsworthy papers:

Nature: Gene implicated in germ-cell development

Methods: Disrupting viruses

Nature: microRNA implicated in cell fate decisions

Geoscience: Methane bubbling up

Neuroscience: Action representation in the autistic brain

Genetics: A common susceptibility locus for several types of cancer

Cell Biology: Getting to the root of oculo-facial-cardio-dental syndrome

Chemical Biology: Glutathione analogue discovered

Nature: A tale of two spores

And finally…Immunology: Specialized skin helpers

· Mention of papers to be published at the same time with the same embargo

· Geographical listing of authors

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[1] Nature: Gene implicated in germ-cell development
DOI: 10.1038/nature08210

A screening method using cultured, differentiated mouse embryonic stem (ES) cells has identified Lin28 as an important gene in the formation of germ cells – progenitors of egg and sperm cells. The study, reported in this week's Nature, highlights the use of cultured stem cells for determining key genes involved in important biological processes, such as the development of egg and sperm, and cancer.

George Daley and colleagues differentiated mouse ES cells into putative primordial germ cells, the early embryonic precursors of egg and sperm. They then used short inhibitory RNA strands to switch off key genes, a technique that highlighted Lin28 as a possible player in germ-cell formation.

To confirm their suspicions, ES cells lacking Lin28 were injected into developing mouse embryos where they then failed to form germ cells in the chimaeric animals. Overexpressing Lin28, by contrast, enhanced the formation of germ cells in chimaeric animals. The team also showed that Lin28 levels are raised in primary human germ-cell tumours. Overall, the study suggests that Lin28 is a novel regulator of germ-cell development and a possible player in germ-cell malignancy.

Author contact:
George Daley (Children's Hospital Boston, MA, USA)
Tel: +1 617 919 2013; E-mail: [email protected]

[2] Methods: Disrupting viruses
DOI 10.1038/nmeth.1346

A technique to reversibly disrupt viral proteins is reported online this week in Nature Methods. It will allow for the study of viral protein function, a prerequisite for the design of antiviral substances, such as drugs or antibodies.

The study of viral genes essential for infection is difficult because strains with deletions or mutations in these genes fail to grow. Martin Messerle and colleagues have tackled this problem not at the level of the gene but at the protein level. They adapt a method originally developed to induce protein instability in mammalian cells, to the large family of herpes viruses.

The technique is based on fusing a destabilizing peptide to the protein of interest. This fusion protein is immediately degraded unless the destabilizing peptide is bound by a small synthetic ligand that shields the protein and allows it to exert its normal function. Removal and re-addition of the ligand allow conditional and reversible disruption of the fusion proteins.

By adapting this strategy for viruses the team opens the door for detailed studies of protein function in herpes viruses and other viral families.

Author contact:
Martin Messerle (Hannover Medical School, Germany)
Tel: +49 5115 32 4320; E-mail: [email protected]

[3] Nature: microRNA implicated in cell fate decisions
DOI: 10.1038/nature01895

Two microRNAs, single-stranded RNA fragments known to influence gene expression, have been shown to regulate cell fate decisions. The findings may have implications for the generation of induced pluripotent stem cells.

One of the microRNAs, miR-145, triggers the differentiation of neural crest stem cells into vascular smooth muscle, and is also needed to reprogram adult fibroblasts into smooth muscle cells, Deepak Srivastava and colleagues report online this week in Nature. The findings are evidence that a single microRNA can efficiently coax stem cells to form a specific cell type, and regulate the reprogramming of cells into an alternative fate.

The team also shows that miR-145 and another microRNA, miR-143, help repress proliferation and promote differentiation of smooth muscle cells. The two microRNAs target a network of transcription factors that includes Klf4, one of the key ingredients in the recipe to induce pluripotent stem (iPS) cells. iPS cells - mature cells reprogrammed into a stem cell-like state - are attractive because they represent an ethical, potentially patient-matched source of stem cells.

Author contact:
Deepak Srivastava (University of California at San Francisco, CA, USA)
Tel: +1 415 734 2716; E-mail: [email protected]

[4] Geoscience: Methane bubbling up
DOI: 10.1038/ngeo574

Substantial amounts of the greenhouse gas methane can reach the surface ocean from seafloor seeps as deep as 600 metres, shows a study online in Nature Geoscience this week. The results indicate that current estimates of the global flux of methane from the oceans to the atmosphere may be too low.

Using a submersible robotic vehicle, Evan Solomon and colleagues directly sampled methane concentrations in bubble plumes at several sites in the Gulf of Mexico between 500 and 600 metres depth, where the gas emanates from seafloor vents. The researchers suggest that the transfer of methane to the atmosphere from the investigated deepwater plumes is 10 to 1,000 times higher than the amounts previously estimated for shallow-water seeps. This is contrary to the idea that only methane from shallow-water seeps reaches the ocean surface in significant amounts.

The researchers suggest that seeps in similar active hydrocarbon basins, such as the Persian Gulf, Caspian Sea, West African Margin and the Alaska North Slope, should be investigated more closely to improve estimates of the global methane flux from the oceans to the atmosphere.

Author contact:
Evan Solomon (Scripps Institution of Oceanography, La Jolla, CA, USA)
Tel: +1 858 534 4857; E-mail: [email protected]

[5] Neuroscience: Action representation in the autistic brain
DOI: 10.1038/nn.2356

Children with autism rely more on internal cues about the orientation of their limbs when learning to use a novel tool in new situations, reports a study published online this week in Nature Neuroscience. In contrast, children without autism rely equally on external cues, such as vision. The study found that greater reliance on internal cues in the autistic group correlated with greater impairments in social functioning and imitation.

Reza Shadmehr and colleagues asked groups of autistic and non-autistic children to move a robotic ‘arm’ towards a target. The robotic arm was designed to resist their movements, so that the first attempts were disjointed and off-target; though with practice both groups quickly learned to compensate for this.

The team then noted how well the children could generalize this learned adjustment to new target locations. Two types of target locations were tested: one required the children to rotate their hand and arm joints in way that was identical to what had been learnt, though the movements looked quite different; the other required movements which looked similar to what had been learnt, but joint rotations required were different. Shadmehr and colleagues discovered that autistic children only utilized the previous learned adjustments when joint rotations were the same, whereas the non-autistic children adjusted to both types of targets

Generalized learning based on what movements look like relies on visual cues, whereas the generalized learning exhibited by the autistic children – which is based on joint rotations – requires a greater awareness of internal cues about the position of limbs in space.

Author contact:
Reza Shadmehr (Johns Hopkins University, Baltimore, MD, USA)
Tel. +1 410 614 2458; E-mail: [email protected]

[6], [7], [8]. [9] & [10] Genetics: A common susceptibility locus for several types of cancer
DOI: 10.1038/ng 407
DOI: 10.1038/ng.411
DOI: 10.1038/ng.410
DOI: 10.1038/ng.412
DOI: 10.1038/ng.408

Genetic variants near two genes on the chromosomal locus 9p21 increase the risk for multiple types of cancer, including glioma, basal cell carcinoma, and melanoma, according to five independent studies published online in this week’s Nature Genetics.

Studies by Richard Houlston, Margaret Wrensch and colleagues discovered new risk variants for glioma—a type of brain cancer that typically has a poor prognosis. Including the genetic variant near the genes CDKN2A and CDKN2B on chromosome 9p21, this new research found five new loci that are associated with increased risk of glioma.

Basal cell carcinoma (BCC) is a common type of non-melanoma skin cancer. The primary environmental risk factor for BCC is sun exposure, although genetic susceptibility also plays an important role in determining risk. Simon Stacey and colleagues identify a risk variant for BCC near CDKN2A and CDKN2B as well as two new risk variants on other chromosomes.

Finally, Tim Spector, Timothy Bishop and colleagues identified a susceptibility locus for melanoma near the genes CDKN2A and CDKN2B. Similar to BCC, repeated sun exposure and familial history of the disease increase the risk of developing melanoma. These studies also report three other genetic variants that are associated with increased risk of melanoma.

Author contacts:
Richard Houlston (Institute of Cancer Research, Sutton, UK) Author paper [6]
Tel: +44 208 722 4175; E-mail: [email protected]

Melissa Bondy (University of Texas M. D. Anderson Cancer Center, Houston, TX, USA) co-Author paper [6]
Tel: +1 713 794 5264; E-mail: [email protected]

Timothy Bishop (University of Leeds, UK) Author paper [7]
Tel: +44 113 206 4573; E-mail: [email protected]

Tim Spector (Kings College, London, UK) Author paper [8]
Tel: +44 20 7188 6765; E-mail: [email protected]

Simon Stacey (deCODE, Reykjavik, Iceland) Author paper [9]
Tel: +354 570 2880; Email: [email protected]

Edward Farmer (deCODE, Reykjavik, Iceland) Media contact paper [9]
Tel: +44 7796 010107; Email: [email protected]

Margaret Wrensch (University of California at San Francisco, CA, USA) Author paper [10]
Tel: +1 415 476 1979; E-mail: [email protected]

[11] Cell Biology: Getting to the root of oculo-facial-cardio-dental syndrome
DOI: 10.1038/ncb1913

An insight into the underlying causes of oculo-facial-cardio-dental syndrome (OFCD) – a rare genetic disorder characterized by elongated roots of teeth, craniofacial, cardiac and eye abnormalities – is provided online this week in Nature Cell Biology. The study could help shed light on the process that causes this disease.

Mutations in BCOR, a protein associated with shutting down gene expression during fetal development, are known to be associated with OFCD, but how disrupting BCOR function results in the defects seen in OFCD is not known. Cun-Yu Wang and colleagues show that mesenchymal stem cells isolated from the tooth roots of OFCD patients have an enhanced tendency to develop into dental and bone cells. Expressing BCOR in these cells can reverse this phenomenon. Removing BCOR from healthy mesenchymal stem cells was found to also result in increased formation of bone and dental cells.

The authors also show that transcription factor that is known to play a role in craniofacial development, is highly expressed in mesenchymal stem cells from OFCD patients’ teeth roots. Removing this factor from the cells reverses their enhanced tendency to develop into dental and bone cells, indicating that this transcription factor is responsible for these changes.

These findings provide a molecular explanation for the exaggerated dental and craniofacial features seen in patients with OFCD.

Author contact:
Cun-Yu Wang (University of California at Los Angeles, CA, USA)
Tel: +1 310 825 4415; E-mail: [email protected]

[12] Chemical Biology: Glutathione analogue discovered
DOI: 10.1038/nchembio.189

A new chemical compound which works in an analogous way as the antioxidant glutathione is reported online this week in Nature Chemical Biology. The research explains how some bacteria regulate intracellular conditions, and will have major implications on understanding bacterial cell function.

Glutathione is a short peptide that contains a thiol group – a sulfur atom that can easily switch between being bonded to a hydrogen atom, in the ‘reduced’ state, or another sulfur atom in the ‘oxidized’ state. The number of peptides in the reduced or oxidized state has consequences for what other reactions can occur in the cell. Glutathione is not present in many bacteria, making it unclear how they regulate these processes.

Robert Fahey and colleagues have identified bacillithiol as a new natural product that contains a thiol group linked to a sugar residue. This compound, present in Bacillus species and other bacteria, helps explain how these bacteria control their cellular state. This will enable further studies into the proteins that make and regulate bacillithiol.

Author contact:
Robert Fahey (University of California at San Diego, La Jolla, CA, USA)
Tel: +1 858 534 2163; E-mail: [email protected]

[13] Nature: A tale of two spores
DOI: 10.1038/nature08150

Discrete changes in morphology may occur via gradual evolutionary changes due to ‘partial penetrance,’ a genetic phenomenon where a given mutation produces detectable symptoms only in a fraction of the individuals carrying it. The finding, reported in this week’s Nature, helps to explain how the puzzling phenomenon of partial penetrance works.

Partial penetrance can generate different fates with different frequencies, but the underlying mechanism is unclear. Michael Elowitz and colleagues systematically explored the random and genetic factors controlling the outcome of partially penetrant mutations in the spore-producing bacterium Bacillus subtilis. The results suggest that progressive increases in the penetrance of mutations affecting DNA replication and cell division act together to aid the development of twin, rather than single, spores as a new trait.

Author contact:
Michael Elowitz (California Institute of Technology, Pasadena, CA, USA)
Tel: +1 626 395 8871; E-mail: [email protected]

[14] & [15] Immunology: Specialized skin helpers
DOI: 10.1038/ni.1767
DOI: 10.1038/ni.1770

A new type of immune cell that is dedicated to combating skin infections is identified in two papers published online in this week’s Nature Immunology. The work could potentially prove useful in the development of treatments for skin conditions such as psoriasis and atopic dermatitis.

Specialized cells, known as TH-22 cells, have been identified which release a chemical mediator called interleukin 22 (IL-22) that has previously been linked to skin inflammation and wound healing. Teams led by Federica Sallusto and Hergen Spits both show that these TH-22 cells express receptors CCR6, CCR4 and CCR10 that direct the cells to the skin. Federica Sallusto and colleagues further show TH-22 cells are generated by unique immune presenting cells called plasmacytoid cells via the release of chemical mediators called IL-6 and groups of certain signaling molecules.

Both authors suggest a vicious cycle can arise if these TH-22 cells are remain switched on and might contribute to skin diseases such as psoriasis and atopic dermatitis.

Author contacts:
Federica Sallusto (Institute for Research in Biomedicine, Bellinzona, Switzerland) Author paper [14]
Tel: +41 918 200 315; E-mail: [email protected]

Hergen Spits (Genentech, South San Francisco, CA, USA) Author paper [15]
Tel: +1 650 227 7712; E-mail: [email protected]

Items from other Nature journals to be published online at the same time and with the same embargo:

Nature (

[16] The AP-1 transcription factor Batf controls TH17 differentiation
DOI: 10.1038/nature08114

[17] Structure of a prokaryotic virtual proton pump at 3.2Å resolution
DOI: 10.1038/nature08201


[18] Synergistic drug combinations tend to improve therapeutically relevant selectivity
DOI: 10.1038/nbt.1549

[19] Quantification of the yeast transcriptome by single-molecule sequencing
DOI: 10.1038/nbt.1551


[20] Histone levels are regulated by phosphorylation and ubiquitylation-dependent proteolysis
DOI: 10.1038/ncb1903

[21] Mitochondrial fission factor Drp1 is essential for embryonic development and synapse formation in mice
DOI: 10.1038/ncb1907

[22] Reversible acetylation of the chromatin remodelling complex NoRC is required for non-coding RNA-dependent silencing
DOI: 10.1038/ncb1914


[23] Zebrafish chemical screening reveals an inhibitor of Dusp6 that expands cardiac cell lineages
DOI: 10.1038/nchembio.190


[24] New insights into the structure and reduction of graphite oxide
DOI: 10.1038/nchem.281

[25] Visualizing and identifying single atoms using electron energy-loss spectroscopy with low accelerating voltage
DOI: 10.1038/nchem.282


[26] Engineering light absorption in semiconductor nanowire devices
DOI: 10.1038/nmat2477

[27] Three-dimensional nanopillar-array photovoltaics on low-cost and flexible substrates
DOI: 10.1038/nmat2493

[28] Organic electronics for precise delivery of neurotransmitters to modulate mammalian sensory function
DOI: 10.1038/nmat2494

[29] Plasmonic analogue of electromagnetically induced transparency at the Drude damping limit
DOI: 10.1038/nmat2495


[30] TGF-b1–induced migration of bone mesenchymal stem cells couples bone resorption with formation
DOI: 10.1038/nm.1979

[31] A small molecule blocking oncogenic protein EWS-FLI1 interaction with RNA helicase A inhibits growth of Ewing's sarcoma
DOI: 10.1038/nm.1983

[32] Alefacept promotes co-stimulation blockade based allograft survival in nonhuman primates
DOI: 10.1038/nm.1993


[33] Mass spectrometry of intact membrane transporters reveals subunit stoichiometry and interactions
DOI: 10.1038/nmeth.1347


[34] Partial sequencing of a single DNA molecule with a scanning tunnelling microscope
DOI: 10.1038/nnano.2009.155

[35] Measurement of the quantum capacitance of graphene
DOI: 10.1038/nnano.2009.177


[36] Disparity- and velocity-based signals for three-dimensional motion perception in human MT+
DOI: 10.1038/nn.2343

[37] Synaptic inhibition of Purkinje cells mediates consolidation of vestibulo-cerebellar motor learning
DOI: 10.1038/nn.2348

[38] Genetic identification of an embryonic parafacial oscillator coupling to the preBotzinger complex
DOI: 10.1038/nn.2354


[39] Pressure-assisted tip-enhanced Raman imaging at a resolution of a few nanometres

Nature PHYSICS (

[40] Appearance of a fractional Stokes–Einstein relation in water and a structural interpretation of its onset
DOI: 10.1038/nphys1328

[41] Measurement of single-molecule frictional dissipation in a prototypical nanoscale system
DOI: 10.1038/nphys1335

[42] Coherent manipulation of Bose–Einstein condensates with state-dependent microwave potentials on an atom chip
DOI: 10.1038/nphys1329

[43] Field-sensitive addressing and control of field-insensitive neutral-atom qubits
DOI: 10.1038/nphys1330


The following list of places refers to the whereabouts of authors on the papers numbered in this release. The listing may be for an author's main affiliation, or for a place where they are working temporarily. Please see the PDF of the paper for full details.

Brisbane: 7, 8
Herston: 7
Melbourne: 7
Westmead: 7

Vienna: 9

Antwerp: 30

Montreal: 8

Beijing: 11, 35
Hubei: 30
Shihezi: 30

Evry: 6
Gif-sur-Yvette: 38
Paris: 6, 7, 38, 42
Villejuif: 7

Bonn: 6
Hannover: 2
Heidelberg: 9, 22
Kaiserslautern: 29
Munich: 42
Stuttgart: 29

Budapest: 9

Reykjavik: 9

Haifa: 41
Tel-Aviv: 7

Cesena: 7
Genova: 7
Messina: 40
Milan: 9
Turin: 37

Fukuoka: 21
Kodarira: 21
Kyoto: 28
Osaka: 21, 34, 39
Saitama: 39
Sasebo: 21
Sendai: 40
Tokyo: 21, 25
Tsukuba: 25

Amsterdam: 37
Leiden: 7
Nijmegen: 9
Rotterdam: 9, 37

Szczecin: 7

Cluj: 9

Banska Bystrica: 9
Ljubljana: 7

Gyeonggi: 26

Barcelona: 7
Huesca: 9
Valencia: 9
Zaragoza: 9

Linkoping: 28
Lund: 7
Norrkoping: 28
Stockholm: 9, 28, 38
Umea: 6

Bellinzona: 14
Zurich: 6

Aberdeen: 37
Cambridge: 1, 8, 33, 41
Durham: 33
Glasgow: 7
Grenoble: 41
Herts: 8
Leeds: 6, 7, 8
London: 8, 37
Norwich: 12
Nottingham: 6
Oxford: 33
Surrey: 6
Sutton: 6


Birmingham: 16, 30

Phoenix: 7
Tempe: 35

Berkeley: 27
Fresno: 12
La Jolla: 4, 12, 15
Los Angeles: 11
Oakland: 10
Pasadena: 13
San Francisco: 3, 10, 11, 15
Santa Barbara: 4
Stanford: 26

Middletown: 40
New Haven: 17

District of Columbia
Washington: 31

Tallahassee: 20

Atlanta: 32

Lewiston: 43

Baltimore: 5, 7
Bethesda: 7, 32
Gaithersburg: 43

Boston: 1, 18, 40
Cambridge: 18, 19
Waltham: 17

Minneapolis: 9
Rochester: 10

St Louis: 16

New Hampshire
Lebanon: 9

New York
Ithaca: 12
New York: 13, 31, 40
Rochester: 3

North Carolina
Winston-Salem: 12

Philadelphia: 7, 8, 13
Pittsburgh: 23

Austin: 36
Corpus Christi: 4
Houston: 6, 24

Salt Lake City: 7

Harrisonburg: 23


For media inquiries relating to embargo policy for all the Nature Research Journals:

Rachel Twinn (Nature London)
Tel: +44 20 7843 4658; E-mail: [email protected]

Neda Afsarmanesh (Nature New York)
Tel: +1 212 726 9231; E-mail: [email protected]

Ruth Francis (Head of Press, Nature, London)
Tel: +44 20 7843 4562; E-mail: [email protected]

For media inquiries relating to editorial content/policy for the Nature Research Journals, please contact the journals individually:

Nature Biotechnology (New York)
Craig Mak
Tel: +1 212 726 9284; E-mail: [email protected]

Nature Cell Biology (London)
Bernd Pulverer
Tel: +44 20 7843 4892; E-mail: [email protected]

Nature Chemical Biology (Boston)
Andrea Garvey
Tel: +1 617 475 9241, E-mail: [email protected]

Nature Chemistry (London)
Stuart Cantrill
Tel: +44 20 7014 4018; E-mail: [email protected]

Nature Genetics (New York)
Myles Axton
Tel: +1 212 726 9324; E-mail: [email protected]

Nature Geoscience (London)
Heike Langenberg
Tel: +44 20 7843 4042; E-mail: [email protected]

Nature Immunology (New York)
Laurie Dempsey
Tel: +1 212 726 9372; E-mail: [email protected]

Nature Materials (London)
Vincent Dusastre
Tel: +44 20 7843 4531; E-mail: [email protected]

Nature Medicine (New York)
Juan Carlos Lopez
Tel: +1 212 726 9325; E-mail: [email protected]

Nature Methods (New York)
Hugh Ash
Tel: +1 212 726 9627; E-mail: [email protected]

Nature Nanotechnology (London)
Peter Rodgers
Tel: +44 20 7014 4019; Email: [email protected]

Nature Neuroscience (New York)
Kalyani Narasimhan
Tel: +1 212 726 9319; E-mail: [email protected]

Nature Photonics (Tokyo)
Oliver Graydon
Tel: +81 3 3267 8776; E-mail: [email protected]

Nature Physics (London)
Alison Wright
Tel: +44 20 7843 4555; E-mail: [email protected]

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Published: 05 Jul 2009

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