Laser‐capture microdissection and transcriptional profiling of the dorsomedial nucleus of the hypothalamus

Lee, Syann; Bookout, Angie L.; Lee, Charlotte E.; Gautron, Laurent; Harper, Matthew; Elias, Carol F.; Lowell, Bradford B.; Elmquist, Joel K.

doi:10.1002/cne.23116

Cited by 24 publications

(27 citation statements)

References 99 publications

(124 reference statements)

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“…This is consistent with our previous finding that NPW mRNA is not detected in the adult DMH (Tanaka et al, 2003). Furthermore, this observation is supported by results from microarray analysis using RNA from adult mouse DMH in which no expression of NPW was detected (Draper et al, 2010;Lee et al, 2012).…”

Section: Discussionsupporting

confidence: 94%

Transient expression of neuropeptide W in postnatal mouse hypothalamus – A putative regulator of energy homeostasis

et al. 2015

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Neuropeptide B and W (NPB and NPW) are cognate peptide ligands for NPBWR1 (GPR7), a G protein-coupled receptor. In rodents, they have been implicated in the regulation of energy homeostasis, neuroendocrine/autonomic responses, and social interactions. Although localization of these peptides and their receptors in adult rodent brain has been well documented, their expression in mouse brain during development is unknown. Here we demonstrate the transient expression of NPW mRNA in the dorsomedial hypothalamus (DMH) of postnatal mouse brain and its co-localization with neuropeptide Y (NPY) mRNA. Neurons expressing both NPW and NPY mRNAs begin to emerge in the DMH at about postnatal day 0 (P-0) through P-3. Their expression is highest around P-14, declines after P-21, and by P-28 only a faint expression of NPW and NPY mRNA remains. In P-18 brains, we detected NPW neurons in the region spanning the subincertal nucleus (SubI), the lateral hypothalamic (LH) perifornical (PF) areas, and the DMH, where the highest expression of NPW mRNA was observed. The majority of these postnatal hypothalamic NPW neurons co-express NPY mRNA. A cross of NPW-iCre knock-in mice with a Cre-dependent tdTomato reporter line revealed that more than half of the reporter-positive neurons in the adult DMH, which mature from the transiently NPW-expressing neurons, are sensitive to peripherally administrated leptin. These data suggest that the DMH neurons that transiently co-express NPW and NPY in the peri-weaning period might play a role in regulating energy homeostasis during postnatal development.

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Section: Discussionsupporting

confidence: 94%

Transient expression of neuropeptide W in postnatal mouse hypothalamus – A putative regulator of energy homeostasis

et al. 2015

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“…Yoshida et al [68] observed that SCN neurons innervate the HCRT field medial to the fornix. The multiplicity of regional inputs to the HCRT field and heterogeneity of LH/DMH cell populations [71], [72] and activation patterns [73], [74] suggest that both direct and indirect SCN inputs may regulate Per1 expression in this region.…”

Section: Discussionmentioning

confidence: 99%

Central Control of Circadian Phase in Arousal-Promoting Neurons

2013

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Cells of the dorsomedial/lateral hypothalamus (DMH/LH) that produce hypocretin (HCRT) promote arousal in part by activation of cells of the locus coeruleus (LC) which express tyrosine hydroxylase (TH). The suprachiasmatic nucleus (SCN) drives endogenous daily rhythms, including those of sleep and wakefulness. These circadian oscillations are generated by a transcriptional-translational feedback loop in which the Period (Per) genes constitute critical components. This cell-autonomous molecular clock operates not only within the SCN but also in neurons of other brain regions. However, the phenotype of such neurons and the nature of the phase controlling signal from the pacemaker are largely unknown. We used dual fluorescent in situ hybridization to assess clock function in vasopressin, HCRT and TH cells of the SCN, DMH/LH and LC, respectively, of male Syrian hamsters. In the first experiment, we found that Per1 expression in HCRT and TH oscillated in animals held in constant darkness with a peak phase that lagged that in AVP cells of the SCN by several hours. In the second experiment, hamsters induced to split their locomotor rhythms by exposure to constant light had asymmetric Per1 expression within cells of the middle SCN at 6 h before activity onset (AO) and in HCRT cells 9 h before and at AO. We did not observe evidence of lateralization of Per1 expression in the LC. We conclude that the SCN communicates circadian phase to HCRT cells via lateralized neural projections, and suggests that Per1 expression in the LC may be regulated by signals of a global or bilateral nature.

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“…Slides were then dehydrated in a graded ethanol series followed by 5 minutes in xylenes. The Arcturus Veritas Microdissection System (Molecular Devices) was used to isolate each nucleus based on defined neuroanatomical boundaries 30 as described previously 31 . Nuclei collected are listed in Supplementary Table 4.…”

Section: Methodsmentioning

confidence: 99%

“…Due to sufficiently high expression, it was not necessary to pre-amplify 18S rRNA, which was used as the normalizer gene. All gene expression levels were measured with an Applied Biosystems 7900HT Sequence Detection System using the efficiency-corrected ΔCt method as previously described 31,32 . The anatomic specificity of the LCM dissections was confirmed by QPCR for the expression of known marker genes in each nucleus.…”

Section: Methodsmentioning

confidence: 99%

FGF21 regulates metabolism and circadian behavior by acting on the nervous system

Bookout

Groot

Owen

et al. 2013

Nat Med

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461

482

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Fibroblast growth factor 21 (FGF21) is a hepatokine that acts as a global starvation signal to modulate fuel partitioning and metabolism, and repress growth1; however the site of action of these diverse effects remains unclear. FGF21 signals through a heteromeric cell surface receptor composed of one of three FGF receptors (FGFR1c, 2c, or 3c) in complex with β-Klotho2-4, a single-pass transmembrane protein that is enriched in metabolic tissues5. Here we show that in addition to its known effects on peripheral metabolism, FGF21 increases systemic glucocorticoid levels, suppresses physical activity, and alters circadian behavior, all features of the adaptive starvation response. These effects are mediated through β-Klotho expression in the suprachiasmatic nucleus (SCN) of the hypothalamus and the dorsal vagal complex (DVC) of the hindbrain. Mice lacking the β-Klotho gene (Klb) in these regions are refractory to these effects, as well as those on metabolism, insulin, and growth. These findings demonstrate a crucial role for the nervous system in mediating the diverse physiologic and pharmacologic actions of FGF21.

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Laser‐capture microdissection and transcriptional profiling of the dorsomedial nucleus of the hypothalamus

Cited by 24 publications

References 99 publications

Transient expression of neuropeptide W in postnatal mouse hypothalamus – A putative regulator of energy homeostasis

Transient expression of neuropeptide W in postnatal mouse hypothalamus – A putative regulator of energy homeostasis

Central Control of Circadian Phase in Arousal-Promoting Neurons

FGF21 regulates metabolism and circadian behavior by acting on the nervous system

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