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Requirement for RORgamma in thymocyte survival and lymphoid organ development (2000)

Z. Sun ; D. Unutmaz ; Y. R. Zou ; [et al.]

American Association for the Advancement of Science (AAAS)

In: Science. 288(5475): 2369-73.

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Publication Date: 2000-07-06

Description: Most developing thymocytes undergo apoptosis because they cannot interact productively with molecules encoded by the major histocompatibility complex. Here, we show that mice lacking the orphan nuclear hormone receptor RORgamma lose thymic expression of the anti-apoptotic factor Bcl-xL. RORgamma thus regulates the survival of CD4+8+ thymocytes and may control the temporal window during which thymocytes can undergo positive selection. RORgamma was also required for development of lymph nodes and Peyer's patches, but not splenic follicles. In its absence, there was loss of a population of CD3-CD4+CD45+ cells that normally express RORgamma and that are likely early progenitors of lymphoid organs. Hence, RORgamma has critical functions in T cell repertoire selection and lymphoid organogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sun, Z -- Unutmaz, D -- Zou, Y R -- Sunshine, M J -- Pierani, A -- Brenner-Morton, S -- Mebius, R E -- Littman, D R -- New York, N.Y. -- Science. 2000 Jun 30;288(5475):2369-73.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine and Howard Hughes Medical Institute, New York University School of Medicine, New York, NY 10016, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10875923" target="_blank"〉PubMed〈/a〉

Keywords: Animals ; Apoptosis ; *CDC2-CDC28 Kinases ; Cell Count ; Cell Cycle ; Cell Survival ; Crosses, Genetic ; Cyclin-Dependent Kinase 2 ; Cyclin-Dependent Kinases/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Female ; Gene Targeting ; Inhibitor of Differentiation Protein 2 ; Lymphoid Tissue/cytology/embryology/*growth & development ; Male ; Mice ; Mice, Inbred C57BL ; Nuclear Receptor Subfamily 1, Group F, Member 3 ; Protein-Serine-Threonine Kinases/metabolism ; Proto-Oncogene Proteins c-bcl-2/genetics/metabolism ; Receptors, Cytoplasmic and Nuclear/genetics/*physiology ; *Receptors, Retinoic Acid ; *Receptors, Thyroid Hormone ; *Repressor Proteins ; T-Lymphocyte Subsets/*cytology ; Thymus Gland/*cytology ; *Transcription Factors ; bcl-X Protein

Print ISSN: 0036-8075

Electronic ISSN: 1095-9203

Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics

Published by American Association for the Advancement of Science (AAAS)

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Dual-mode operation of neuronal networks involved in left-right alternation (2013)

A. E. Talpalar ; J. Bouvier ; L. Borgius ; [et al.]

Nature Publishing Group (NPG)

In: Nature. 500(7460): 85-8. doi: 10.1038/nature12286.

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Publication Date: 2013-07-03

Description: All forms of locomotion are repetitive motor activities that require coordinated bilateral activation of muscles. The executive elements of locomotor control are networks of spinal neurons that determine gait pattern through the sequential activation of motor-neuron pools on either side of the body axis. However, little is known about the constraints that link left-right coordination to locomotor speed. Recent advances have indicated that both excitatory and inhibitory commissural neurons may be involved in left-right coordination. But the neural underpinnings of this, and a possible causal link between these different groups of commissural neurons and left-right alternation, are lacking. Here we show, using intersectional mouse genetics, that ablation of a group of transcriptionally defined commissural neurons--the V0 population--leads to a quadrupedal hopping at all frequencies of locomotion. The selective ablation of inhibitory V0 neurons leads to a lack of left-right pattern at low frequencies, mixed coordination at medium frequencies, and alternation at high locomotor frequencies. When ablation is targeted to excitatory V0 neurons, left-right alternation is present at low frequencies, and hopping is restricted to medium and high locomotor frequencies. Therefore, the intrinsic logic of the central control of locomotion incorporates a modular organization, with two subgroups of V0 neurons required for the existence of left-right alternating modes at different speeds of locomotion. The two molecularly distinct sets of commissural neurons may constrain species-related naturally occurring frequency-dependent coordination and be involved in the evolution of different gaits.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Talpalar, Adolfo E -- Bouvier, Julien -- Borgius, Lotta -- Fortin, Gilles -- Pierani, Alessandra -- Kiehn, Ole -- England -- Nature. 2013 Aug 1;500(7460):85-8. doi: 10.1038/nature12286. Epub 2013 Jun 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Mammalian Locomotor Laboratory, Department of Neuroscience, Karolinska Institutet, Stockholm S-17177, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23812590" target="_blank"〉PubMed〈/a〉

Keywords: Animals ; Extremities/*physiology ; Functional Laterality/genetics/*physiology ; Gait/genetics/physiology ; Homeodomain Proteins/genetics/metabolism ; Locomotion/genetics/*physiology ; Mice ; Nerve Net/*physiology ; Neural Inhibition ; Neurons/*physiology ; Spinal Nerves/cytology/physiology

Print ISSN: 0028-0836

Electronic ISSN: 1476-4687

Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics