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1529-240127502007Dec12The Journal of neuroscience : the official journal of the Society for NeuroscienceJ NeurosciThe neonatal ventromedial hypothalamus transcriptome reveals novel markers with spatially distinct patterning.136241363413624-34The ventromedial hypothalamus (VMH) is a distinct morphological nucleus involved in feeding, fear, thermoregulation, and sexual activity. It is essentially unknown how VMH circuits underlying these innate responses develop, in part because the VMH remains poorly defined at a cellular and molecular level. Specifically, there is a paucity of cell-type-specific genetic markers with which to identify neuronal subgroups and manipulate development and signaling in vivo. Using gene profiling, we now identify approximately 200 genes highly enriched in neonatal (postnatal day 0) mouse VMH tissue. Analyses of these VMH markers by real or virtual (Allen Brain Atlas; http://www.brain-map.org) experiments revealed distinct regional patterning within the newly formed VMH. Top neonatal markers include transcriptional regulators such as Vgll2, SF-1, Sox14, Satb2, Fezf1, Dax1, Nkx2-2, and COUP-TFII, but interestingly, the highest expressed VMH transcript, the transcriptional coregulator Vgll2, is completely absent in older animals. Collective results from zebrafish knockdown experiments and from cellular studies suggest that a subset of these VMH markers will be important for hypothalamic development and will be downstream of SF-1, a critical factor for normal VMH differentiation. We show that at least one VMH marker, the AT-rich binding protein Satb2, was responsive to the loss of leptin signaling (Lep(ob/ob)) at postnatal day 0 but not in the adult, suggesting that some VMH transcriptional programs might be influenced by fetal or early postnatal environments. Our study describing this comprehensive "VMH transcriptome" provides a novel molecular toolkit to probe further the genetic basis of innate neuroendocrine behavioral responses.KurraschDeborah MDMDepartment of Physiology, University of California, San Francisco, San Francisco, California 94143, USA.CheungClement CCCLeeFlorence YFYTranPhu VPVHataKenjiKIngrahamHolly AHAengR01 DK063592DKNIDDK NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't
United StatesJ Neurosci81021400270-64740Biomarkers0Homeobox Protein Nkx-2.20Leptin0Matrix Attachment Region Binding Proteins0Muscle Proteins0Nkx2-2 protein, mouse0RNA, Messenger0SATB2 protein, mouse0Steroidogenic Factor 10Transcription Factors0Vgll2 protein, mouse0Zebrafish Proteins0nkx2.2b protein, zebrafishIMAge FactorsAnimalsAnimals, NewbornBiomarkersmetabolismCell DifferentiationgeneticsEmbryo, NonmammalianGene Expression ProfilingGene Expression Regulation, DevelopmentalgeneticsHomeobox Protein Nkx-2.2Hypothalamuscytologygrowth & developmentmetabolismLeptinmetabolismMaleMatrix Attachment Region Binding ProteinsgeneticsmetabolismMiceMice, Mutant StrainsMuscle ProteinsgeneticsRNA, MessengermetabolismSignal TransductiongeneticsSteroidogenic Factor 1geneticsmetabolismTranscription FactorsgeneticsmetabolismZebrafishZebrafish Proteins200712149020081239020071214902008612ppublish18077674PMC667362610.1523/JNEUROSCI.2858-07.200727/50/13624Altman J, Bayer SA. 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