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{"title"=>"DLK1 is a somato-dendritic protein expressed in hypothalamic arginine-vasopressin and oxytocin neurons", "type"=>"journal", "authors"=>[{"first_name"=>"Carine", "last_name"=>"Villanueva", "scopus_author_id"=>"24467107400"}, {"first_name"=>"Sandrine", "last_name"=>"Jacquier", "scopus_author_id"=>"9842579900"}, {"first_name"=>"Nicolas", "last_name"=>"de Roux", "scopus_author_id"=>"6701665764"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"22563444", "doi"=>"10.1371/journal.pone.0036134", "sgr"=>"84860354289", "isbn"=>"1932-6203 (Electronic)\\n1932-6203 (Linking)", "scopus"=>"2-s2.0-84860354289", "issn"=>"19326203", "pui"=>"364709161"}, "id"=>"dfba2884-be81-3bd0-aac5-ae39fee54fda", "abstract"=>"Delta-Like 1 Homolog, Dlk1, is a paternally imprinted gene encoding a transmembrane protein involved in the differentiation of several cell types. After birth, Dlk1 expression decreases substantially in all tissues except endocrine glands. Dlk1 deletion in mice results in pre-natal and post-natal growth deficiency, mild obesity, facial abnormalities, and abnormal skeletal development, suggesting involvement of Dlk1 in perinatal survival, normal growth and homeostasis of fat deposition. A neuroendocrine function has also been suggested for DLK1 but never characterised. To evaluate the neuroendocrine function of DLK1, we first characterised Dlk1 expression in mouse hypothalamus and then studied post-natal variations of the hypothalamic expression. Western Blot analysis of adult mouse hypothalamus protein extracts showed that Dlk1 was expressed almost exclusively as a soluble protein produced by cleavage of the extracellular domain. Immunohistochemistry showed neuronal DLK1 expression in the suprachiasmatic (SCN), supraoptic (SON), paraventricular (PVN), arcuate (ARC), dorsomedial (DMN) and lateral hypothalamic (LH) nuclei. DLK1 was expressed in the dendrites and perikarya of arginine-vasopressin neurons in PVN, SCN and SON and in oxytocin neurons in PVN and SON. These findings suggest a role for DLK1 in the post-natal development of hypothalamic functions, most notably those regulated by the arginine-vasopressin and oxytocin systems.", "link"=>"http://www.mendeley.com/research/dlk1-somatodendritic-protein-expressed-hypothalamic-argininevasopressin-oxytocin-neurons", "reader_count"=>15, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Researcher"=>3, "Student > Ph. D. Student"=>6, "Other"=>1, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Researcher"=>3, "Student > Ph. D. Student"=>6, "Other"=>1, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>8, "Medicine and Dentistry"=>3, "Psychology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>8}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"United States"=>1}, "group_count"=>2}

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• http://doi.org/10.1111/jne.12029
• http://doi.org/10.1111/eva.12244
• http://doi.org/10.1146/annurev-neuro-061010-113708
• http://doi.org/10.1371/journal.pbio.1001952
• http://doi.org/10.1111/jne.12172
• http://doi.org/10.1111/jne.12507
• http://doi.org/10.1210/en.2017-00122
• http://doi.org/10.1146/annurev-physiol-021113-170347
• http://doi.org/10.1210/jc.2016-3677
• http://doi.org/10.1016/j.anbehav.2014.02.013
• http://doi.org/10.1210/jc.2018-02010
• http://doi.org/10.1016/j.cytogfr.2019.03.006
• http://doi.org/10.1371/journal.pone.0116088
• http://doi.org/10.1016/j.neubiorev.2017.05.004
• http://doi.org/10.20945/2359-3997000000164

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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/646961"], "description"=>"<p>Dual immunofluorescence staining for DLK1 (C-19) and phosphorylated neurofilament (SMI-31) or microtubule-associated protein 2 (MAP-2) on free-floating sections of hypothalami from adult male mice. Tissue was fixed and processed as described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036134#s2\" target=\"_blank\">materials and methods</a>. Arrowheads indicate co-staining of DLK1 and MAP-2 in dendrites and perykarya. DLK1 do not colocalize with SMI-31 (40× objective for MAP-2 and 63× objective for SMI-31, scale bar: 10 µm).</p>", "links"=>[], "tags"=>["restricted", "dendrites", "perikarya", "hypothalamic"], "article_id"=>317453, "categories"=>["Chemistry", "Molecular Biology", "Biochemistry", "Developmental Biology"], "users"=>["Carine Villanueva", "Sandrine Jacquier", "Nicolas de Roux"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036134.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DLK1_expression_is_restricted_to_dendrites_and_perikarya_of_hypothalamic_neurons_/317453", "title"=>"DLK1 expression is restricted to dendrites and perikarya of hypothalamic neurons.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-26 02:04:13"}
• {"files"=>["https://ndownloader.figshare.com/files/647179"], "description"=>"<p>Dual immunofluorescence staining of DLK1 (antibody C-19) and AVP or OXT on 0.6 µm-thick confocal PVN (A), SCN (B) and SON (C) sections obtained using a 63× objective. Arrowheads indicate double staining. Scale bars: 10 µm.</p>", "links"=>[], "tags"=>["avp", "oxt", "neurons", "scn"], "article_id"=>317673, "categories"=>["Chemistry", "Molecular Biology", "Biochemistry", "Developmental Biology"], "users"=>["Carine Villanueva", "Sandrine Jacquier", "Nicolas de Roux"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036134.g005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DLK1_expression_in_AVP_and_OXT_neurons_in_the_PVN_the_SCN_and_the_SON_/317673", "title"=>"DLK1 expression in AVP and OXT neurons in the PVN, the SCN and the SON.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-26 02:07:53"}
• {"files"=>["https://ndownloader.figshare.com/files/646873"], "description"=>"<p><b>A</b>) Immunohistochemistry using the C-19 antibody was performed on free-floating coronal brain sections from adult male mice as described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036134#s2\" target=\"_blank\">materials and methods</a> (2,5× objective; Bregma −0.82 mm at the hypothalamic level according to the mouse brain atlas <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036134#pone.0036134-Franklin1\" target=\"_blank\">[21]</a>. B) Bregma −2.06 mm C) Higher magnification of the paraventricular nucleus (PVN), suprachiasmatic nucleus (SCN), supraoptic nucleus (SON) arcuate nucleus (ARC), and lateral hypothalamic nucleus (LH) (20× objective; scale bar: 80 µm).</p>", "links"=>[], "tags"=>["nuclei"], "article_id"=>317370, "categories"=>["Chemistry", "Molecular Biology", "Biochemistry", "Developmental Biology"], "users"=>["Carine Villanueva", "Sandrine Jacquier", "Nicolas de Roux"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036134.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DLK1_is_expressed_in_specific_nuclei_of_the_hypothalamus_/317370", "title"=>"DLK1 is expressed in specific nuclei of the hypothalamus.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-26 02:02:50"}
• {"files"=>["https://ndownloader.figshare.com/files/333122", "https://ndownloader.figshare.com/files/333160", "https://ndownloader.figshare.com/files/333231", "https://ndownloader.figshare.com/files/333294"], "description"=>"<div><p>Delta-Like 1 Homolog, <em>Dlk1</em>, is a paternally imprinted gene encoding a transmembrane protein involved in the differentiation of several cell types. After birth, <em>Dlk1</em> expression decreases substantially in all tissues except endocrine glands. <em>Dlk1</em> deletion in mice results in pre-natal and post-natal growth deficiency, mild obesity, facial abnormalities, and abnormal skeletal development, suggesting involvement of <em>Dlk1</em> in perinatal survival, normal growth and homeostasis of fat deposition. A neuroendocrine function has also been suggested for DLK1 but never characterised. To evaluate the neuroendocrine function of DLK1, we first characterised <em>Dlk1</em> expression in mouse hypothalamus and then studied post-natal variations of the hypothalamic expression. Western Blot analysis of adult mouse hypothalamus protein extracts showed that <em>Dlk1</em> was expressed almost exclusively as a soluble protein produced by cleavage of the extracellular domain. Immunohistochemistry showed neuronal DLK1 expression in the suprachiasmatic (SCN), supraoptic (SON), paraventricular (PVN), arcuate (ARC), dorsomedial (DMN) and lateral hypothalamic (LH) nuclei. DLK1 was expressed in the dendrites and perikarya of arginine-vasopressin neurons in PVN, SCN and SON and in oxytocin neurons in PVN and SON. These findings suggest a role for DLK1 in the post-natal development of hypothalamic functions, most notably those regulated by the arginine-vasopressin and oxytocin systems.</p> </div>", "links"=>[], "tags"=>["dlk1", "somato-dendritic", "expressed", "hypothalamic", "arginine-vasopressin", "oxytocin", "neurons"], "article_id"=>125784, "categories"=>["Chemistry", "Molecular Biology", "Biochemistry", "Developmental Biology"], "users"=>["Carine Villanueva", "Sandrine Jacquier", "Nicolas de Roux"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0036134.s001", "https://dx.doi.org/10.1371/journal.pone.0036134.s002", "https://dx.doi.org/10.1371/journal.pone.0036134.s003", "https://dx.doi.org/10.1371/journal.pone.0036134.s004"], "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/DLK1_Is_a_Somato_Dendritic_Protein_Expressed_in_Hypothalamic_Arginine_Vasopressin_and_Oxytocin_Neurons/125784", "title"=>"DLK1 Is a Somato-Dendritic Protein Expressed in Hypothalamic Arginine-Vasopressin and Oxytocin Neurons", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-04-26 01:36:24"}
• {"files"=>["https://ndownloader.figshare.com/files/646775"], "description"=>"<p>(A) Reverse-transcription polymerase chain reaction (RT-PCR) was performed using two primers located in <i>Dlk1</i> exons 4 and 5 as described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036134#s2\" target=\"_blank\">materials and methods</a>. (B) Schematic representation of the DLK1-A and C2 isoforms. The arrows indicate the proteolytic cleavage sites described by Smas et al. <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036134#pone.0036134-Smas1\" target=\"_blank\">[5]</a>. The dark grey boxes indicate epidermal growth factor (EGF)-like repeats. SP: signal peptide region. TMD: transmembrane domain. JMD: juxtamembrane domain. ECD: extracellular domain. ICD: intracellular domain. (C) Western blot on total proteins extracted from adult male mouse hypothalamus and pituitary. (D) Pituitary and hypothalamic DLK1 isoforms were characterized in post-nuclear supernatants (PNS) and membrane extracts (M). DLK1 isoforms were detected using a goat polyclonal anti-DLK1 antibody against the intracellular domain (C-19) and a rabbit polyclonal anti-DLK1 antibody against part of the extracellular domain, the transmembrane and the intracellular domain (H-118). NP, non-proteolysed DLK1.</p>", "links"=>[], "tags"=>["hypothalamus", "pituitary", "uncleaved", "cleaved"], "article_id"=>317267, "categories"=>["Chemistry", "Molecular Biology", "Biochemistry", "Developmental Biology"], "users"=>["Carine Villanueva", "Sandrine Jacquier", "Nicolas de Roux"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036134.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DLK1_expression_in_the_adult_male_mouse_hypothalamus_and_pituitary_as_uncleaved_and_cleaved_proteins_/317267", "title"=>"DLK1 expression in the adult male mouse hypothalamus and pituitary as uncleaved and cleaved proteins.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-26 02:01:07"}
• {"files"=>["https://ndownloader.figshare.com/files/647043"], "description"=>"<p>A) Total hypothalamic RNA was extracted on post-natal days 6, 20 and 60 (P6, P20, P60). mRNA levels were quantified using real-time RT-PCR as described in the <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036134#s2\" target=\"_blank\">materials and methods</a> section. The graphs show fold increases in expression at P20 and P60 compared to P6. <i>Kiss1</i> expression was quantified using real-time RT-PCR as described in the <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036134#s2\" target=\"_blank\">materials and methods</a> section. The graphs represent pooled data (mean ± SEM) from three different experiments with 4 mice per group. *indicates a significant increase (<i>p</i><0.01) relative to P6. B) DLK1 protein levels on P6, P20 and P60 were evaluated using western blot on total cellular extracts with the H-118 antibody.</p>", "links"=>[], "tags"=>["increases", "hypothalamus"], "article_id"=>317535, "categories"=>["Chemistry", "Molecular Biology", "Biochemistry", "Developmental Biology"], "users"=>["Carine Villanueva", "Sandrine Jacquier", "Nicolas de Roux"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036134.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Dlk1_expression_increases_in_the_hypothalamus_between_birth_and_adulthood_/317535", "title"=>"<i>Dlk1</i> expression increases in the hypothalamus between birth and adulthood.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-26 02:05:35"}

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Relative Metric

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F1000Prime