Dlx5 and Dlx6 expression in GABAergic neurons controls behavior, metabolism, healthy aging and lifespan
Open accessPublished version of a preprint
Abstract
ABSTRACT Dlx5 and Dlx6 encode two homeobox transcription factors expressed by developing and mature GABAergic interneurons. During development Dlx5/6 are important for the differentiation of Parvalbumin ( Pvalb )-expressing neurons. Perinatal lethality of homozygous mice in which Dlx5/6 have been constitutively deleted has, so far, hindered the study of the function of these genes in adult neurons. We first show that Dlx5 and Dlx6 are expressed by all subclasses of adult cortical GABAergic neurons. Then we analyse Vgat ΔDlx5-6 mice in which Dlx5 and Dlx6 are simultaneously inactivated in all GABAergic interneurons. Vgat ΔDlx5-6 mice present a behavioral pattern suggesting reduction of anxiety and obsessive-compulsive activities. They rapidly access and spend more time in the central region of an open field, bury few marbles in the marble burying test and show little interest in nest building. Male and female 20-month-old Vgat ΔDlx5-6 animals have the same size as their normal littermates, but present a 25% body weight reduction associated with a marked decline in white and brown adipose tissue. Remarkably, both Vgat ΔDlx5-6/+ and Vgat ΔDlx5-6 mice present a 33% longer median survival than their control littermates. Hallmarks of biological aging such as motility, adipose deposition and coat conditions are improved in mutant animals. Our data imply that GABAergic interneurons can regulate mammalian healthspan and lifespan through Dlx5/6 -dependent mechanisms. Understanding these regulations can be an entry point to unravel the processes through which the brain affects body homeostasis and, ultimately, longevity and healthy aging. SIGNIFICANCE STATEMENT Dlx5 and Dlx6 are transcription factors controlling several developmental processes, including GABAergic neuronal migration and differentiation. To study their function in adult brain, we selectively inactivated both genes in GABAergic interneurons ( Vgat ΔDlx5-6 mice). Mutant mice have reduced anxiety-like and obsessive-compulsive behaviors. Interestingly, Vgat ΔDlx5-6 mice have a 25% body weight reduction and about 70% less white and brown adipose tissue; their general health status is excellent. Vgat ΔDlx5-6 mice have a median survival about 33% longer than their control littermates and hallmarks of biological aging are improved. Dlx5/6-dependent regulations in GABAergic neurons could be an entry point to understand how the brain determines the psychophysiological status of the body and, ultimately, longevity and healthy aging.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Social behavior between individuals of the same genotype was very variable, resulting in no significant difference in sociability between control, Dlx5/6VgatCre/+ and Dlx5/6VgatCre mice.
“Social behavior between individuals of the same genotype was very variable, resulting in no significant difference in sociability between control, Dlx5/6VgatCre/+ and Dlx5/6VgatCre mice (de Lombares, et al. 2019).”
From <i>DLX5/6</i> GABAergic Expression Affects Social Vocalization: Implications for Human Evolution (2021) · cites this paper as de Lombares, et al. 2019
The Results section, “Sociability tests” (page unavailable), reports no significant difference between control, heterozygous and homozygous mutant mice in one sociability test, and no difference between genotypes in a second test. It does not say that behavior varied greatly among mice of the same genotype or that such variability caused the lack of a significant difference. (LLM, conf=0.86)
Experimental — accuracy not yet measuredTargeted inactivation of Dlx5/6 in mouse GABAergic neurons results in behavioral and metabolic phenotypes including a 33% increase in lifespan.
“Targeted inactivation of Dlx5/6 in mouse GABAergic neurons (Dlx5/6VgatCre mice) results in behavioral and metabolic phenotypes notably increasing lifespan by 33%.”
From <i>DLX5/6</i> GABAergic Expression Affects Social Vocalization: Implications for Human Evolution (2021) · cites this paper as de Lombares, et al. 2019
Underrepresentation of DLX5/6-N-Haplotype in semi-supercentenarians suggests an association between DLX5/6 brain expression and healthy aging.
“suggesting an association between DLX5/6 brain expression and healthy aging reminiscent of what has been shown in mouse models (de Lombares, et al. 2019).”
From <i>DLX5/6</i> GABAergic Expression Affects Social Vocalization: Implications for Human Evolution (2021) · cites this paper as de Lombares, et al. 2019
The underrepresentation of DLX5/6-N-Haplotype in semi-supercentenarians could be related to the 33% lifespan extension described for Dlx5/6VgatCre mice, suggesting that the DLX5/6-N-Haplotype could regulate DLX5/6 neuronal expression.
“This observation could be related to the 33% lifespan extension described for Dlx5/6VgatCre mice, suggesting that the DLX5/6-N-Haplotype could regulate DLX5/6 neuronal expression (de Lombares, et al. 2019).”
From <i>DLX5/6</i> GABAergic Expression Affects Social Vocalization: Implications for Human Evolution (2021) · cites this paper as de Lombares, et al. 2019
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets.
Macosko, E. Z., Basu, A., Satija, R., Nemesh, J., Shekhar, K., Goldman, M., Tirosh, I., Bialas, A. R., Kamitaki, N., Martersteck, E. M., et al. (2015) · Cell · doi:10.1016/j.cell.2015.05.002 · Cited by 7,110 · see citing works
Extending Healthy Life Span—From Yeast to Humans
Fontana, L., Partridge, L., & Longo, V. D. (2010) · Science · doi:10.1126/science.1172539 · Cited by 3,023 · see citing works
Risks of all-cause and suicide mortality in mental disorders: a meta-review
Chesney, E., Goodwin, G. M., & Fazel, S. (2014) · World Psychiatry · doi:10.1002/wps.20128 · Cited by 2,115 · see citing works
Neuronal Diversity and Temporal Dynamics: The Unity of Hippocampal Circuit Operations
Klausberger, T., & Somogyi, P. (2008) · Science · doi:10.1126/science.1149381 · Cited by 2,050 · see citing works
GABAergic Interneurons in the Neocortex: From Cellular Properties to Circuits
Tremblay, R., Lee, S., & Rudy, B. (2016) · Neuron · doi:10.1016/j.neuron.2016.06.033 · Cited by 2,033 · see citing works
Molecular diversity and specializations among the cells of the adult mouse brain
Saunders, A., Macosko, E. Z., Wysoker, A., Goldman, M., Krienen, F. M., de Rivera, H., Bien, E., Baum, M., Bortolin, L., Wang, S., et al. (2018) · Cell · doi:10.1016/j.cell.2018.07.028 · Cited by 1,847 · cited 3× · see citing works
“Single-cell RNA sequencing (scRNA-seq) analysis was performed on publicly available datasets where individual cells from adult frontal cortex were profiled using Drop-seq technology (GEO accession number GSE116470) [36].”
MethodResultShared and distinct transcriptomic cell types across neocortical areas
Tasic, B., Yao, Z., Graybuck, L. T., Smith, K. A., Nguyen, T. N., Bertagnolli, D., Goldy, J., Garren, E., Economo, M. N., Viswanathan, S., et al. (2018) · Nature · doi:10.1038/s41586-018-0654-5 · Cited by 1,746 · see citing works
Leptin Action on GABAergic Neurons Prevents Obesity and Reduces Inhibitory Tone to POMC Neurons
Vong, L., Ye, C., Yang, Z., Choi, B. J., Chua, S. C., & Lowell, B. B. (2011) · Neuron · doi:10.1016/j.neuron.2011.05.028 · Cited by 1,238 · see citing works
Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes
Chao, H.-T., Chen, H., Samaco, R. C., Xue, M., Chahrour, M., Yoo, J., Neul, J. L., Gong, S., Lu, H.-C., Heintz, N., et al. (2010) · Nature · doi:10.1038/nature09582 · Cited by 1,168 · see citing works
Age-dependent DNA methylation of genes that are suppressed in stem cells is a hallmark of cancer
Teschendorff, A. E., Menon, U., Gentry-Maharaj, A., Ramus, S. J., Weisenberger, D. J., Shen, H., Campan, M., Noushmehr, H., Bell, C. G., Maxwell, A. P., et al. (2010) · Genome Research · doi:10.1101/gr.103606.109 · Cited by 855 · see citing works
Aging of blood can be tracked by DNA methylation changes at just three CpG sites
Weidner, C. I., Lin, Q., Koch, C., Eisele, L., Beier, F., Ziegler, P., Bauerschlag, D., Jöckel, K., Erbel, R., Mühleisen, T., et al. (2014) · Genome Biology · doi:10.1186/gb-2014-15-2-r24 · Cited by 849 · see citing works
Neuronal cell-type classification: challenges, opportunities and the path forward
Zeng, H., & Sanes, J. R. (2017) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.85 · Cited by 841 · see citing works
Bell, J., Tsai, P.-C., Yang, T.-P., Pidsley, R., Nisbet, J. P., Glass, D., Mangino, M., Zhai, G., Zhang, F., Valdes, A., et al. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002629 · Cited by 722 · see citing works
Development and Functional Diversification of Cortical Interneurons
Lim, L., Mi, D., Llorca, A., & Marín, O. (2018) · Neuron · doi:10.1016/j.neuron.2018.10.009 · Cited by 714 · cited 1× · see citing works
“Brain activity depends on GABAergic inhibitory interneurons, a heterogeneous class of neurons distinguished by diverse anatomical, biochemical and physiological characteristics [1].”
BackgroundSensory Detection of Food Rapidly Modulates Arcuate Feeding Circuits
Chen, Y., Lin, Y.-C., Kuo, T.-W., & Knight, Z. A. (2015) · Cell · doi:10.1016/j.cell.2015.01.033 · Cited by 660 · see citing works
Origins of Cortical Interneuron Subtypes
Xu, Q., Cobos, I., De La Cruz, E., Rubenstein, J. L., & Anderson, S. A. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.5667-03.2004 · Cited by 639 · see citing works
Single-Cell RNA-Seq Reveals Hypothalamic Cell Diversity
Chen, R., Wu, X., Jiang, L., & Zhang, Y. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.03.004 · Cited by 592 · see citing works
The temporal and spatial origins of cortical interneurons predict their physiological subtype
Butt, S. J. B., Fuccillo, M., Nery, S., Noctor, S., Kriegstein, A., Corbin, J. G., & Fishell, G. (2005) · Neuron · doi:10.1016/j.neuron.2005.09.034 · Cited by 587 · see citing works
Loss of silent-chromatin looping and impaired imprinting of DLX5 in Rett syndrome
Horike, S., Cai, S., Miyano, M., Cheng, J., & Kohwi-shigematsu, T. (2004) · Nature Genetics · doi:10.1038/ng1491 · Cited by 585 · see citing works
Bulfone, A., Puelles, L., Porteus, M. H., FROHMAN, M., Martin, G. R., & Rubenstein, J. L. R. (1993) · Journal of Neuroscience · doi:10.1523/jneurosci.13-07-03155.1993 · Cited by 574 · see citing works
Developmental functions of theDistal-less/Dlx homeobox genes
Panganiban, G. E. F., & Rubenstein, J. L. R. (2002) · Development · doi:10.1242/dev.129.19.4371 · Cited by 522 · see citing works
Developmental diversification of cortical inhibitory interneurons
Mayer, C., Hafemeister, C., Bandler, R. C., Machold, R., Batista Brito, R., Jaglin, X., Allaway, K., Butler, A., Fishell, G., & Satija, R. (2018) · Nature · doi:10.1038/nature25999 · Cited by 492 · see citing works
Integrative analysis of the cancer transcriptome
Rhodes, D. R., & Chinnaiyan, A. M. (2005) · Nature Genetics · doi:10.1038/ng1570 · Cited by 490 · see citing works
Specification of Jaw Subdivisions by Dlx Genes
Depew, M. J., Lufkin, T., & Rubenstein, J. L. R. (2002) · Science · doi:10.1126/science.1075703 · Cited by 468 · see citing works
Craniofacial, vestibular and bone defects in mice lacking the Distal-less-related gene Dlx5
Acampora, D., Merlo, G. R., Paleari, L., Zerega, B., Postiglione, M. P., Mantero, S., Bober, E., Barbieri, O., Simeone, A., & Levi, G. (1999) · Development · doi:10.1242/dev.126.17.3795 · Cited by 444 · see citing works
Self-citationTranscriptional Architecture of Synaptic Communication Delineates GABAergic Neuron Identity
Paul, A., Crow, M., Raudales, R., He, M., Gillis, J., & Huang, Z. J. (2017) · Cell · doi:10.1016/j.cell.2017.08.032 · Cited by 421 · see citing works
DNA methylation pattern changes upon long‐term culture and aging of human mesenchymal stromal cells
Bork, S., Pfister, S. M., Witt, H., Horn, P., Korn, B., Ho, A. D., & Wagner, W. (2009) · Aging Cell · doi:10.1111/j.1474-9726.2009.00535.x · Cited by 411 · see citing works
The origin and migration of cortical neurones: new vistas
Parnavelas, J. G. (2000) · Trends in Neurosciences · doi:10.1016/s0166-2236(00)01553-8 · Cited by 393 · see citing works
Marble Burying and Nestlet Shredding as Tests of Repetitive, Compulsive-like Behaviors in Mice
Angoa‐Pérez, M., Kane, M. J., Briggs, D. I., Francescutti, D. M., & Kuhn, D. M. (2013) · Journal of Visualized Experiments · doi:10.3791/50978 · Cited by 391 · see citing works
Prader-Willi syndrome: advances in genetics, pathophysiology and treatment
Goldstone, A. P. (2003) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2003.11.003 · Cited by 388 · see citing works
Dlx5 regulates regional development of the branchial arches and sensory capsules
Depew, M. J., Liu, J. K., Long, J. E., Presley, R., Meneses, J. J., Pedersen, R. A., & Rubenstein, J. L. R. (1999) · Development · doi:10.1242/dev.126.17.3831 · Cited by 364 · see citing works
Zerucha, T., Stühmer, T., Hatch, G., Park, B. K., Long, Q., Yu, G. K., Gambarotta, A., Schultz, J. R., Rubenstein, J. L. R., & Ekker, M. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-02-00709.2000 · Cited by 360 · see citing works
Cho, K. K. A., Hoch, R., Lee, A. T., Patel, T., Rubenstein, J. L. R., & Sohal, V. S. (2015) · Neuron · doi:10.1016/j.neuron.2015.02.019 · Cited by 329 · see citing works
Anderson, S. A. (1999) · Cerebral Cortex · doi:10.1093/cercor/9.6.646 · Cited by 325 · see citing works
DLX-1, DLX-2, and DLX-5 expression define distinct stages of basal forebrain differentiation
Eisenstat, D. D., Liu, J. K., Mione, M., Zhong, W., Yu, G. K., Anderson, S. A., Ghattas, I. R., Puelles, L., & Rubenstein, J. L. R. (1999) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19991115)414:2 · Cited by 286 · see citing works
Cloning and characterization of two members of the vertebrate Dlx gene family.
Simeone, A., Acampora, D., Pannese, M., D’Esposito, M., Stornaiuolo, A., Gulisano, M., Mallamaci, A., Kastury, K., Druck, T., & Huebner, K. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.6.2250 · Cited by 277 · see citing works
Hypothalamic Agrp Neurons Drive Stereotypic Behaviors beyond Feeding
Dietrich, M. O., Zimmer, M. R., Bober, J., & Horváth, T. L. (2015) · Cell · doi:10.1016/j.cell.2015.02.024 · Cited by 271 · see citing works
Ronn, T., Volkov, P., Gillberg, L., Kokosar, M., Perfilyev, A., Jacobsen, A. L., Jorgensen, S. W., Brons, C., Jansson, P.-A., Eriksson, K.-F., et al. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv124 · Cited by 270 · see citing works
Ectopic expression of the Dlx genes induces glutamic acid decarboxylase and Dlx expression
Stühmer, T., Anderson, S. A., Ekker, M., & Rubenstein, J. L. R. (2002) · Development · doi:10.1242/dev.129.1.245 · Cited by 257 · see citing works
de Chaumont, F., Ey, E., Torquet, N., Lagache, T., Dallongeville, S., Imbert, A., Legou, T., Sourd, A. L., Fauré, P., Bourgeron, T., et al. (2019) · Nature Biomedical Engineering · doi:10.1038/s41551-019-0396-1 · Cited by 235 · see citing works
Self-citationMetabolic syndrome and mental illness.
Newcomer, J. W. (2007) · PubMed · Cited by 233 · see citing works
The Necdin Gene is Deleted in Prader-Willi Syndrome and is Imprinted in Human and Mouse
MacDonald, H. R., & Wevrick, R. (1997) · Human Molecular Genetics · doi:10.1093/hmg/6.11.1873 · Cited by 230 · see citing works
Role of Prelimbic GABAergic Circuits in Sensory and Emotional Aspects of Neuropathic Pain
Zhang, Z., Gadotti, V. M., Chen, L., Souza, I. A., Stemkowski, P. L., & Zamponi, G. W. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.07.001 · Cited by 229 · see citing works
Liu, J. K., Ghattas, I. R., Liu, S., Chen, S., & Rubenstein, J. L. R. (1997) · Developmental Dynamics · doi:10.1002/(sici)1097-0177(199712)210:4 · Cited by 217 · see citing works
Porteus, M. H., Bulfone, A., Ciaranello, R. D., & Rubenstein, J. L. R. (1991) · Neuron · doi:10.1016/0896-6273(91)90260-7 · Cited by 208 · see citing works
Expression from a Dlx Gene Enhancer Marks Adult Mouse Cortical GABAergic Neurons
Stühmer, T. (2002) · Cerebral Cortex · doi:10.1093/cercor/12.1.75 · Cited by 198 · see citing works
Jaw transformation with gain of symmetry after Dlx5/Dlx6 inactivation: Mirror of the past?
Beverdam, A., Merlo, G. R., Paleari, L., Mantero, S., Genova, F., Barbieri, O., Janvier, P., & Levi, G. (2002) · genesis · doi:10.1002/gene.10156 · Cited by 190 · see citing works
Self-citationDlx5andDlx6Regulate the Development of Parvalbumin-Expressing Cortical Interneurons
Wang, Y., Dye, C. A., Sohal, V. S., Long, J. E., Estrada, R. C., Roztocil, T., Lufkin, T., Deisseroth, K. A., Baraban, S. C., & Rubenstein, J. L. R. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.5963-09.2010 · Cited by 186 · see citing works
Necdin Promotes GABAergic Neuron Differentiation in Cooperation with Dlx Homeodomain Proteins
Kuwajima, T., Nishimura, I., & Yoshikawa, K. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.1262-06.2006 · Cited by 163 · see citing works
Multiple functions of Dlx genes
Merlo, G. R., Zerega, B., Paleari, L., Trombino, S., Mantero, S., & Levi, G. (2000) · The International Journal of Developmental Biology · doi:10.1387/ijdb.11061425 · Cited by 162 · see citing works
Self-citationGAD2 on Chromosome 10p12 Is a Candidate Gene for Human Obesity
Boutin, P., Christian Dina, C., Vasseur, F., Dubois, S. G., Corset, L., Séron, K., Bekris, L. M., Cabellon, J., NEVE, B. P., Vasseur-Delannoy, V., et al. (2003) · PLoS Biology · doi:10.1371/journal.pbio.0000068 · Cited by 149 · see citing works
DLX5 Regulates Development of Peripheral and Central Components of the Olfactory System
Long, J. E., Garel, S., Depew, M. J., Tobet, S. A., & Rubenstein, J. L. R. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-02-00568.2003 · Cited by 131 · see citing works
Gene Expression in Cortical Interneuron Precursors is Prescient of their Mature Function
Batista‐Brito, R., Machold, R. P., Klein, C., & Fishell, G. (2008) · Cerebral Cortex · doi:10.1093/cercor/bhm258 · Cited by 130 · see citing works
Xu, Z., & Taylor, J. A. (2013) · Carcinogenesis · doi:10.1093/carcin/bgt391 · Cited by 129 · see citing works
Nousen, E. K., Franco, J. G., & Sullivan, E. L. (2013) · Neuroendocrinology · doi:10.1159/000355632 · Cited by 123 · see citing works
Woo, T.-U. W., Kim, A. M., & Viscidi, E. (2008) · Brain Research · doi:10.1016/j.brainres.2008.03.092 · Cited by 122 · see citing works
Developmental Mechanisms Underlying the Generation of Cortical Interneuron Diversity
Flames, N., & Marín, Ó. (2005) · Neuron · doi:10.1016/j.neuron.2005.04.020 · Cited by 107 · see citing works
Sasaki, A., Masuda, Y. M., Iwaï, K., Ikeda, K., & Watanabe, K. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109728200 · Cited by 104 · see citing works
An Early Phase of EmbryonicDlx5Expression Defines the Rostral Boundary of the Neural Plate
Yang, L., Zhang, H., Hu, G., et al. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-20-08322.1998 · Cited by 104 · see citing works
Enriquez, J., Venkatasubramanian, L., Baek, M., Peterson, M., Aghayeva, U., & Mann, R. S. (2015) · Neuron · doi:10.1016/j.neuron.2015.04.011 · Cited by 95 · see citing works
Distinct DNA methylation patterns of cognitive impairment and trisomy 21 in down syndrome
Jones, M. J., Farré, P., McEwen, L. M., MacIsaac, J. L., Watt, K., Neumann, S., Emberly, E. G., Cynader, M. S., Virji‐Babul, N., & Kobor, M. S. (2013) · BMC Medical Genomics · doi:10.1186/1755-8794-6-58 · Cited by 87 · see citing works
Okita, C., Meguro, M., Hoshiya, H., Haruta, M., Sakamoto, Y., & Oshimura, M. (2003) · Genomics · doi:10.1016/s0888-7543(03)00052-1 · Cited by 81 · see citing works
Fujihara, K., Miwa, H., Kakizaki, T., Kaneko, R., Mikuni, M., Tanahira, C., Tamamaki, N., & Yanagawa, Y. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.117 · Cited by 81 · see citing works
Rizzo, S. J. S., Anderson, L. C., Green, T. L., McGarr, T. C., Wells, G., & Winter, S. S. (2018) · Current Protocols in Mouse Biology · doi:10.1002/cpmo.45 · Cited by 78 · see citing works
The Dlx5 homeodomain gene is essential for olfactory development and connectivity in the mouse
Levi, G., Puché, A. C., Mantero, S., Barbieri, O., Trombino, S., Paleari, L., Egeo, A., & Merlo, G. R. (2003) · Molecular and Cellular Neuroscience · doi:10.1016/s1044-7431(02)00041-6 · Cited by 72 · see citing works
Self-citationAn SNP in an ultraconserved regulatory element affects <i>Dlx5/Dlx6</i> regulation in the forebrain
Poitras, L., Yu, M., Lesage-Pelletier, C., MacDonald, R. B., Gagné, J.-P., Hatch, G., Kelly, I., Hamilton, S. P., Rubenstein, J. L. R., Poirier, G. G., et al. (2010) · Development · doi:10.1242/dev.051052 · Cited by 69 · see citing works
Ge, J., Gao, W.-C., Cheng, W., Lu, W., Tang, J., Peng, L., Li, N., & Chen, F. (2013) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2013.05.007 · Cited by 64 · see citing works
New insight into GABAergic neurons in the hypothalamic feeding regulation
Suyama, S., & Yada, T. (2018) · The Journal of Physiological Sciences · doi:10.1007/s12576-018-0622-8 · Cited by 59 · see citing works
Nishida‐Fukuda, H., Miyagawa, S., Vieux-Rochas, M., Morini, M., Ogino, Y., Suzuki, K., Nakagata, N., Choi, H., Levi, G., & Yamada, G. (2008) · Endocrinology · doi:10.1210/en.2007-1265 · Cited by 58 · see citing works
Self-citationConserved rules in embryonic development of cortical interneurons
Laclef, C., & Métin, C. (2018) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2017.09.017 · Cited by 57 · see citing works
Defective neuronogenesis in the absence of Dlx5
Perera, M., Merlo, G. R., Verardo, S., Paleari, L., Corte, G., & Levi, G. (2004) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2003.10.004 · Cited by 56 · see citing works
Self-citationSupport for the MnlI polymorphism of SNAP25; a Korean ADHD case–control study
Choi, T. K., Lee, H. S., Kim, J. W., Park, T. W., Song, D. H., Yook, K. W., Lee, S. H., Kim, J. I., & Suh, S.-Y. (2002) · Molecular Psychiatry · doi:10.1038/sj.mp.4001922 · Cited by 43 · see citing works
Aging in Prader–Willi syndrome: Twelve persons over the age of 50 years
Sinnema, M., Schrander-Stumpel, C. T. R. M., Maaskant, M. A., Boer, H., & Curfs, L. (2012) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.35333 · Cited by 39 · see citing works
Vieux-Rochas, M., Mantero, S., Heude, É., Barbieri, O., Astigiano, S., Couly, G. F., Kurihara, H., Levi, G., & Merlo, G. R. (2010) · genesis · doi:10.1002/dvg.20625 · Cited by 36 · see citing works
Self-citationDefining the autism minimum candidate gene region on chromosome 7
Hutcheson, H. B., Bradford, Y. M., Folstein, S. E., Gardiner, M., Santangelo, S. L., Sutcliffe, J. S., & Haines, J. L. (2002) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.10033 · Cited by 36 · see citing works
Kimura, M. I., Kazuki, Y., Kashiwagi, A., Kai, Y., Abe, S., Barbieri, O., Levi, G., & Oshimura, M. (2004) · Journal of Human Genetics · doi:10.1007/s10038-004-0139-2 · Cited by 34 · see citing works
Self-citationParnaudeau, S., Dongelmans, M. L., Turiault, M., Ambroggi, F., Delbès, A.-S., Cansell, C., Luquet, S. H., Piazza, P., Tronche, F., & Barik, J. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00035 · Cited by 34 · see citing works
Self-citationBellessort, B., Cardinal, M. L., Bachelot, A., et al. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv452 · Cited by 34 · see citing works
Chen, Z., Xu, Y., Wu, R., Han, Y.-X., Yu, Y., Ge, J., & Chen, F. (2017) · Journal of Neuroendocrinology · doi:10.1111/jne.12462 · Cited by 33 · see citing works
Live Mouse Tracker: real-time behavioral analysis of groups of micePreprint
de Chaumont, F., Ey, E., Torquet, N., Lagache, T., Dallongeville, S., Imbert, A., Legou, T., Lesourd, A., Faure, P., Bourgeron, T., et al. (2018) · bioRxiv · doi:10.1101/345132 · Cited by 32 · see citing works
Self-citationDNA methylation profiles of elderly individuals subjected to indentured childhood labor and trauma
Marinova, Z., Maercker, A. R. A., Küffer, A., Robinson, M. D., Wojdacz, T. K., Walitza, S., Grünblatt, E., & Burri, A. V. (2017) · BMC Medical Genetics · doi:10.1186/s12881-017-0370-2 · Cited by 31 · see citing works
Bouhali, K., Dipietromaria, A., Fontaine, A., et al. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr166 · Cited by 25 · see citing works
Self-citationExpanding neurotransmitters in the hypothalamic neurocircuitry for energy balance regulation
Xu, Y., & Tong, Q. (2011) · Protein & Cell · doi:10.1007/s13238-011-1112-4 · Cited by 20 · see citing works
Increased bone resorption and osteopenia in Dlx5 heterozygous mice
Samee, N., Geoffroy, V. A., Marty, C., et al. (2009) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22188 · Cited by 13 · see citing works
Strategies for Autism Candidate Gene Analysis
Barnby, G., & Monaco, A. P. (2003) · Novartis Foundation symposium · doi:10.1002/0470869380.ch4 · Cited by 12 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
<i>DLX5/6</i> GABAergic Expression Affects Social Vocalization: Implications for Human Evolution
Levi, G., de Lombares, C., Giuliani, C., Iannuzzi, V., Aouci, R., Garagnani, P., Franceschi, C., Grimaud-Hervé, D., & Narboux-Nême, N. (2021) · Molecular Biology and Evolution · doi:10.1093/molbev/msab181 · Cited by 29 · see citing works
Self-citation
- Authors
- de Lombares, C., Heude, E., Alfama, G., Fontaine, A., Hassouna, R., Vernochet, C., de Chaumont, F., Olivo-Marin, C., Ey, E., Parnaudeau, S., Tronche, F., Bourgeron, T., Luquet, S., Levi, G., & Narboux-Nême, N.
- Affiliations
- Physiologie Moléculaire et Adaptation, CNRS UMR7221, Muséum National d’Histoire Naturelle, Département AVIV, Paris, France
- Centre National de la Recherche Scientifique (FR)
- BioImage Analysis Unit, Institut Pasteur, CNRS UMR 3691, Paris, France
- Corresponding author
- Levi, Giovanni
- ORCID
- Venue
- Aging
- Publisher
- Impact Journals, LLC
- Published
- 2019-09-12
- Volume
- 11
- Issue
- 17
- Pages
- 6638-6656
- ISSN
- 1945-4589 (ISSN-L)
- PMC
- PMC6756896
- OpenAlex
- W2972886985
- Cited by
- 52
- References
- 85
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 13 · 2023: 6 · 2022: 7 · 2021: 9 · 2020: 5
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Aging (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- HAL (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-17-CE37-0007, ANR-17-CE14-0024)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Keywords
- Dlx5, Dlx6, GABAergic neurons, lifespan, healthy aging, metabolism, behavior, longevity
- MeSH terms
- Healthy Aging, Animals, Behavior, Animal, Interneurons, Longevity, Homeodomain Proteins, Mice, GABAergic Neurons
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
