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  • 1
    Publication Date: 2011-11-15
    Description: Intestinal epithelial stem cell identity and location have been the subject of substantial research. Cells in the +4 niche are slow-cycling and label-retaining, whereas a different stem cell niche located at the crypt base is occupied by crypt base columnar (CBC) cells. CBCs are distinct from +4 cells, and the relationship between them is unknown, though both give rise to all intestinal epithelial lineages. We demonstrate that Hopx, an atypical homeobox protein, is a specific marker of +4 cells. Hopx-expressing cells give rise to CBCs and all mature intestinal epithelial lineages. Conversely, CBCs can give rise to +4 Hopx-positive cells. These findings demonstrate a bidirectional lineage relationship between active and quiescent stem cells in their niches.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3705713/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3705713/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takeda, Norifumi -- Jain, Rajan -- LeBoeuf, Matthew R -- Wang, Qiaohong -- Lu, Min Min -- Epstein, Jonathan A -- R01 HL071546/HL/NHLBI NIH HHS/ -- U01 HL100405/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2011 Dec 9;334(6061):1420-4. doi: 10.1126/science.1213214. Epub 2011 Nov 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22075725" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Cycle ; Cell Differentiation ; Cell Lineage ; Cell Proliferation ; Cells, Cultured ; Epithelial Cells/*cytology ; Homeodomain Proteins/analysis/genetics ; Intestinal Mucosa/*cytology/drug effects ; Intestine, Small/*cytology/drug effects ; Mice ; Models, Biological ; Multipotent Stem Cells/*cytology/physiology ; Paneth Cells/cytology ; *Stem Cell Niche ; Tamoxifen/pharmacology
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  • 2
    Publication Date: 2011-03-19
    Description: In prokaryotes and eukaryotes, most genes appear to be transcribed during short periods called transcriptional bursts, interspersed by silent intervals. We describe how such bursts generate gene-specific temporal patterns of messenger RNA (mRNA) synthesis in mammalian cells. To monitor transcription at high temporal resolution, we established various gene trap cell lines and transgenic cell lines expressing a short-lived luciferase protein from an unstable mRNA, and recorded bioluminescence in real time in single cells. Mathematical modeling identified gene-specific on- and off-switching rates in transcriptional activity and mean numbers of mRNAs produced during the bursts. Transcriptional kinetics were markedly altered by cis-regulatory DNA elements. Our analysis demonstrated that bursting kinetics are highly gene-specific, reflecting refractory periods during which genes stay inactive for a certain time before switching on again.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Suter, David M -- Molina, Nacho -- Gatfield, David -- Schneider, Kim -- Schibler, Ueli -- Naef, Felix -- New York, N.Y. -- Science. 2011 Apr 22;332(6028):472-4. doi: 10.1126/science.1198817. Epub 2011 Mar 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Sciences III, University of Geneva, 30 Quai Ernest Ansermet, 1211 Geneva, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21415320" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Animals ; Cells, Cultured ; Chromatin/physiology ; Circadian Rhythm/genetics ; Down-Regulation ; *Gene Expression ; Histones/metabolism ; Kinetics ; Luminescent Measurements ; Mice ; Models, Genetic ; NIH 3T3 Cells ; Promoter Regions, Genetic ; Protein Biosynthesis ; RNA, Messenger/genetics/metabolism ; Stochastic Processes ; *Transcription, Genetic ; Transcriptional Activation ; Transgenes ; Up-Regulation
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  • 3
    Publication Date: 2011-03-26
    Description: Axon-dendrite polarization is crucial for neural network wiring and information processing in the brain. Polarization begins with the transformation of a single neurite into an axon and its subsequent rapid extension, which requires coordination of cellular energy status to allow for transport of building materials to support axon growth. We found that activation of the energy-sensing adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway suppressed axon initiation and neuronal polarization. Phosphorylation of the kinesin light chain of the Kif5 motor protein by AMPK disrupted the association of the motor with phosphatidylinositol 3-kinase (PI3K), preventing PI3K targeting to the axonal tip and inhibiting polarization and axon growth.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325765/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325765/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Amato, Stephen -- Liu, Xiuxin -- Zheng, Bin -- Cantley, Lewis -- Rakic, Pasko -- Man, Heng-Ye -- GM41890/GM/NIGMS NIH HHS/ -- GM56203/GM/NIGMS NIH HHS/ -- K99CA133245/CA/NCI NIH HHS/ -- MH07907/MH/NIMH NIH HHS/ -- R00 CA133245/CA/NCI NIH HHS/ -- R01 GM056203/GM/NIGMS NIH HHS/ -- R01 NS014841/NS/NINDS NIH HHS/ -- R01 NS014841-32/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2011 Apr 8;332(6026):247-51. doi: 10.1126/science.1201678. Epub 2011 Mar 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Boston University, 5 Cummington Street, Boston, MA 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21436401" target="_blank"〉PubMed〈/a〉
    Keywords: AMP-Activated Protein Kinases/*metabolism ; Aminoimidazole Carboxamide/analogs & derivatives/pharmacology ; Animals ; Axons/enzymology/*physiology/ultrastructure ; *Cell Polarity/drug effects ; Cells, Cultured ; Hippocampus/cytology/embryology ; Metformin/pharmacology ; Mice ; Microtubule-Associated Proteins/metabolism ; Neurons/cytology/drug effects/enzymology/*physiology ; Phosphatidylinositol 3-Kinase/*metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism ; Rats ; Recombinant Fusion Proteins/metabolism ; Ribonucleotides/pharmacology ; Signal Transduction ; Tissue Culture Techniques
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  • 4
    Publication Date: 2011-04-02
    Description: Heparan and chondroitin sulfate proteoglycans (HSPGs and CSPGs, respectively) regulate numerous cell surface signaling events, with typically opposite effects on cell function. CSPGs inhibit nerve regeneration through receptor protein tyrosine phosphatase sigma (RPTPsigma). Here we report that RPTPsigma acts bimodally in sensory neuron extension, mediating CSPG inhibition and HSPG growth promotion. Crystallographic analyses of a shared HSPG-CSPG binding site reveal a conformational plasticity that can accommodate diverse glycosaminoglycans with comparable affinities. Heparan sulfate and analogs induced RPTPsigma ectodomain oligomerization in solution, which was inhibited by chondroitin sulfate. RPTPsigma and HSPGs colocalize in puncta on sensory neurons in culture, whereas CSPGs occupy the extracellular matrix. These results lead to a model where proteoglycans can exert opposing effects on neuronal extension by competing to control the oligomerization of a common receptor.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3154093/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3154093/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Coles, Charlotte H -- Shen, Yingjie -- Tenney, Alan P -- Siebold, Christian -- Sutton, Geoffrey C -- Lu, Weixian -- Gallagher, John T -- Jones, E Yvonne -- Flanagan, John G -- Aricescu, A Radu -- 090532/Wellcome Trust/United Kingdom -- 10976/Cancer Research UK/United Kingdom -- EY11559/EY/NEI NIH HHS/ -- G0700232/Medical Research Council/United Kingdom -- G0900084/Medical Research Council/United Kingdom -- HD29417/HD/NICHD NIH HHS/ -- R01 EY011559/EY/NEI NIH HHS/ -- R01 EY011559-19/EY/NEI NIH HHS/ -- R37 HD029417/HD/NICHD NIH HHS/ -- R37 HD029417-20/HD/NICHD NIH HHS/ -- Cancer Research UK/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2011 Apr 22;332(6028):484-8. doi: 10.1126/science.1200840. Epub 2011 Mar 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21454754" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Axons/*physiology ; Binding Sites ; Cell Membrane/metabolism ; Cells, Cultured ; Chondroitin Sulfate Proteoglycans/chemistry/*metabolism ; Chondroitin Sulfates/chemistry/metabolism ; Crystallography, X-Ray ; Extracellular Matrix ; Ganglia, Spinal ; Glypicans/metabolism ; Growth Cones/metabolism ; Heparan Sulfate Proteoglycans/chemistry/*metabolism ; Heparitin Sulfate/analogs & derivatives/chemistry/metabolism ; Humans ; Mice ; Models, Biological ; Models, Molecular ; Molecular Sequence Data ; Neurites/physiology ; Neurocan/metabolism ; Protein Conformation ; Protein Multimerization ; Protein Structure, Tertiary ; Receptor-Like Protein Tyrosine Phosphatases, Class 2/*chemistry/*metabolism ; Sensory Receptor Cells/*physiology
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  • 5
    Publication Date: 2011-01-06
    Description: Apicomplexan parasites invade host cells and immediately initiate cell division. The extracellular parasite discharges transmembrane proteins onto its surface to mediate motility and invasion. These are shed by intramembrane cleavage, a process associated with invasion but otherwise poorly understood. Functional analysis of Toxoplasma rhomboid 4, a surface intramembrane protease, by conditional overexpression of a catalytically inactive form produced a profound block in replication. This was completely rescued by expression of the cleaved cytoplasmic tail of Toxoplasma or Plasmodium apical membrane antigen 1 (AMA1). These results reveal an unexpected function for AMA1 in parasite replication and suggest that invasion proteins help to promote parasite switch from an invasive to a replicative mode.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Santos, Joana M -- Ferguson, David J P -- Blackman, Michael J -- Soldati-Favre, Dominique -- MC_U117532063/Medical Research Council/United Kingdom -- U117532063/Medical Research Council/United Kingdom -- Howard Hughes Medical Institute/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2011 Jan 28;331(6016):473-7. doi: 10.1126/science.1199284. Epub 2010 Dec 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, Faculty of Medicine, University of Geneva, 1 rue-Michel Servet, 1211 Geneva 4, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21205639" target="_blank"〉PubMed〈/a〉
    Keywords: Antigens, Protozoan/chemistry/genetics/*metabolism ; Cell Cycle ; Cell Division ; Cell Membrane/metabolism ; Cells, Cultured ; Fibroblasts/parasitology ; Humans ; Membrane Proteins/chemistry/genetics/*metabolism ; Movement ; Mutant Proteins/metabolism ; Plasmodium falciparum ; Protozoan Proteins/chemistry/genetics/*metabolism ; Serine Proteases/genetics/metabolism ; Signal Transduction ; Toxoplasma/cytology/growth & development/*physiology
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  • 6
    Publication Date: 2011-08-06
    Description: Neural circuitry formation depends on the molecular control of axonal projection during development. By screening with fluorophore-assisted light inactivation in the developing mouse brain, we identified cartilage acidic protein-1B as a key molecule for lateral olfactory tract (LOT) formation and named it LOT usher substance (LOTUS). We further identified Nogo receptor-1 (NgR1) as a LOTUS-binding protein. NgR1 is a receptor of myelin-derived axon growth inhibitors, such as Nogo, which prevent neural regeneration in the adult. LOTUS suppressed Nogo-NgR1 binding and Nogo-induced growth cone collapse. A defasciculated LOT was present in lotus-deficient mice but not in mice lacking both lotus- and ngr1. These findings suggest that endogenous antagonism of NgR1 by LOTUS is crucial for normal LOT formation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3244695/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3244695/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sato, Yasufumi -- Iketani, Masumi -- Kurihara, Yuji -- Yamaguchi, Megumi -- Yamashita, Naoya -- Nakamura, Fumio -- Arie, Yuko -- Kawasaki, Takahiko -- Hirata, Tatsumi -- Abe, Takaya -- Kiyonari, Hiroshi -- Strittmatter, Stephen M -- Goshima, Yoshio -- Takei, Kohtaro -- R37 NS033020/NS/NINDS NIH HHS/ -- R37 NS033020-19/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2011 Aug 5;333(6043):769-73. doi: 10.1126/science.1204144.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21817055" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/*physiology ; Binding Sites ; Calcium-Binding Proteins/chemistry/genetics/*metabolism ; Cell Line ; Cells, Cultured ; GPI-Linked Proteins/genetics/metabolism ; Growth Cones/metabolism ; Humans ; Immunohistochemistry ; Ligands ; Mice ; Mice, Inbred ICR ; Myelin Proteins/genetics/*metabolism ; Olfactory Pathways/*cytology/*growth & development/metabolism ; Prosencephalon/embryology/metabolism ; Protein Binding ; Receptors, Cell Surface/genetics/*metabolism ; Signal Transduction
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  • 7
    Publication Date: 2011-09-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Araque, Alfonso -- Navarrete, Marta -- New York, N.Y. -- Science. 2011 Sep 16;333(6049):1587-8. doi: 10.1126/science.1212525.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Instituto Cajal, Consejo Superior de Investigaciones Cientificas, Madrid 28002, Spain. araque@cajal.csic.es〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21921188" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Adenosine Triphosphate/metabolism ; Animals ; Axons/*physiology ; Calcium Signaling ; Cells, Cultured ; Electric Stimulation ; Ganglia, Spinal/cytology ; Glutamic Acid/metabolism ; Myelin Basic Protein/*metabolism ; Myelin Sheath/*physiology ; Neural Stem Cells/cytology/metabolism ; Oligodendroglia/cytology/*metabolism ; Signal Transduction ; Synaptic Transmission ; Synaptic Vesicles/metabolism
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  • 8
    Publication Date: 2011-01-06
    Description: CD4(+) T regulatory cells (T(regs)), which express the Foxp3 transcription factor, play a critical role in the maintenance of immune homeostasis. Here, we show that in mice, T(regs) were most abundant in the colonic mucosa. The spore-forming component of indigenous intestinal microbiota, particularly clusters IV and XIVa of the genus Clostridium, promoted T(reg) cell accumulation. Colonization of mice by a defined mix of Clostridium strains provided an environment rich in transforming growth factor-beta and affected Foxp3(+) T(reg) number and function in the colon. Oral inoculation of Clostridium during the early life of conventionally reared mice resulted in resistance to colitis and systemic immunoglobulin E responses in adult mice, suggesting a new therapeutic approach to autoimmunity and allergy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3969237/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3969237/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Atarashi, Koji -- Tanoue, Takeshi -- Shima, Tatsuichiro -- Imaoka, Akemi -- Kuwahara, Tomomi -- Momose, Yoshika -- Cheng, Genhong -- Yamasaki, Sho -- Saito, Takashi -- Ohba, Yusuke -- Taniguchi, Tadatsugu -- Takeda, Kiyoshi -- Hori, Shohei -- Ivanov, Ivaylo I -- Umesaki, Yoshinori -- Itoh, Kikuji -- Honda, Kenya -- R00 DK085329/DK/NIDDK NIH HHS/ -- R01 AI052359/AI/NIAID NIH HHS/ -- R01 AI056154/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2011 Jan 21;331(6015):337-41. doi: 10.1126/science.1198469. Epub 2010 Dec 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21205640" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Bacterial Agents/pharmacology ; Cecum/microbiology ; Cells, Cultured ; Clostridium/growth & development/*immunology ; Colitis/immunology/pathology/prevention & control ; Colon/*immunology/metabolism/*microbiology ; Feces/microbiology ; Forkhead Transcription Factors/metabolism ; Germ-Free Life ; Immunity, Innate ; Immunoglobulin E/biosynthesis ; Interleukin-10/immunology/metabolism ; Intestinal Mucosa/*immunology/metabolism ; Intestine, Small/immunology ; Metagenome ; Mice ; Mice, Inbred A ; Mice, Inbred BALB C ; Receptors, Pattern Recognition/physiology ; Specific Pathogen-Free Organisms ; T-Lymphocytes, Helper-Inducer/immunology ; T-Lymphocytes, Regulatory/*immunology/metabolism ; Transforming Growth Factor beta/metabolism
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  • 9
    Publication Date: 2011-01-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2011 Jan 7;331(6013):17. doi: 10.1126/science.331.6013.17.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21212329" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Viral/biosynthesis ; Blood/virology ; Cells, Cultured ; DNA Contamination ; Fatigue Syndrome, Chronic/*virology ; Humans ; Mice ; Polymerase Chain Reaction ; Retroviridae Infections/*virology ; Sensitivity and Specificity ; Viremia ; Xenotropic murine leukemia virus-related virus/immunology/*isolation & ; purification/pathogenicity
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  • 10
    Publication Date: 2011-05-28
    Description: Two broad classes of models have been proposed to explain the patterning of the proximal-distal axis of the vertebrate limb (from the shoulder to the digit tips). Differentiating between them, we demonstrate that early limb mesenchyme in the chick is initially maintained in a state capable of generating all limb segments through exposure to a combination of proximal and distal signals. As the limb bud grows, the proximal limb is established through continued exposure to flank-derived signal(s), whereas the developmental program determining the medial and distal segments is initiated in domains that grow beyond proximal influence. In addition, the system we have developed, combining in vitro and in vivo culture, opens the door to a new level of analysis of patterning mechanisms in the limb.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3258580/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3258580/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cooper, Kimberly L -- Hu, Jimmy Kuang-Hsien -- ten Berge, Derk -- Fernandez-Teran, Marian -- Ros, Maria A -- Tabin, Clifford J -- R37 HD032443/HD/NICHD NIH HHS/ -- R37 HD032443-17/HD/NICHD NIH HHS/ -- R37HD032443/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2011 May 27;332(6033):1083-6. doi: 10.1126/science.1199499.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Harvard Medical School, Department of Genetics, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21617075" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Body Patterning ; Cell Proliferation ; Cells, Cultured ; Chick Embryo ; Chondrogenesis ; Culture Media ; Extremities/*embryology ; Fibroblast Growth Factors/metabolism/pharmacology ; Gene Expression Regulation, Developmental ; Homeodomain Proteins/genetics/metabolism ; Limb Buds/cytology/*embryology/metabolism ; Mesoderm/cytology/embryology/metabolism ; Neoplasm Proteins/genetics/metabolism ; Signal Transduction ; Tretinoin/metabolism/pharmacology ; Wnt Proteins/metabolism/pharmacology
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