Malcolm J. Low
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View article: A mammalian tripartite enhancer cluster controls hypothalamic <i>Pomc</i> expression, food intake, and body weight
A mammalian tripartite enhancer cluster controls hypothalamic <i>Pomc</i> expression, food intake, and body weight Open
Food intake and energy balance are tightly regulated by a group of hypothalamic arcuate neurons expressing the proopiomelanocortin ( POMC) gene. In mammals, arcuate-specific POMC expression is driven by two cis -acting transcriptional enha…
View article: Melanocortin receptor agonist melanotan-II microinjected in the nucleus accumbens decreases appetitive and consumptive responding for food
Melanocortin receptor agonist melanotan-II microinjected in the nucleus accumbens decreases appetitive and consumptive responding for food Open
Rationale . Obesity is a major health problem worldwide. An understanding of the factors that drive feeding behaviors is key to the development of pharmaceuticals to decrease appetite and consumption. Proopiomelanocortin (POMC), the melano…
View article: The G209R mutant mouse as a model for human <i>PCSK1</i> polyendocrinopathy
The G209R mutant mouse as a model for human <i>PCSK1</i> polyendocrinopathy Open
PCSK1 encodes an enzyme required for prohormone maturation into bioactive peptides. A striking number of SNPs and rare mutations in PCSK1 are associated with a range of clinical phenotypes. Infants bearing two copies of a catalytically ina…
View article: Author response: Developmental single-cell transcriptomics of hypothalamic POMC neurons reveal the genetic trajectories of multiple neuropeptidergic phenotypes
Author response: Developmental single-cell transcriptomics of hypothalamic POMC neurons reveal the genetic trajectories of multiple neuropeptidergic phenotypes Open
Article Figures and data Abstract Editor's evaluation Introduction Results Discussion Materials and methods Data availability References Decision letter Author response Article and author information Metrics Abstract Proopiomelanocortin (P…
View article: Adult-born proopiomelanocortin neurons derived from Rax-expressing precursors mitigate the metabolic effects of congenital hypothalamic proopiomelanocortin deficiency
Adult-born proopiomelanocortin neurons derived from Rax-expressing precursors mitigate the metabolic effects of congenital hypothalamic proopiomelanocortin deficiency Open
These data demonstrate that Rax+ progenitors generate POMC neurons in sufficient numbers during adulthood to mitigate the metabolic abnormalities of hypothalamic POMC-deficient mice. The findings suggest that adult hypothalamic neurogenesi…
View article: Developmental single-cell transcriptomics of hypothalamic POMC progenitors reveal the genetic trajectories of multiple neuropeptidergic phenotypes
Developmental single-cell transcriptomics of hypothalamic POMC progenitors reveal the genetic trajectories of multiple neuropeptidergic phenotypes Open
Proopiomelanocortin (POMC) neurons of the hypothalamic arcuate nucleus are essential to regulate food intake and energy balance. However, the ontogenetic transcriptional programs that specify the identity and functioning of these neurons a…
View article: Single Nucleus RNA-Sequencing Reveals Overall Conservation of Hypothalamic Cell Identities but Differential Expression of Specific Genes in the <i>Magel2</i> Null Mouse Model of Prader-Willi Syndrome
Single Nucleus RNA-Sequencing Reveals Overall Conservation of Hypothalamic Cell Identities but Differential Expression of Specific Genes in the <i>Magel2</i> Null Mouse Model of Prader-Willi Syndrome Open
Prader-Willi syndrome (PWS) is a genetic disorder affecting 1 in 10,000 to 30,000 live births. Diagnostic features of PWS including insatiable appetite and obesity are well-defined and many are associated with disruption of hypothalamic fu…
View article: <i>Rax</i> Expression Identifies a Novel Cell Type in the Adult Mouse Hypothalamus
<i>Rax</i> Expression Identifies a Novel Cell Type in the Adult Mouse Hypothalamus Open
Hypothalamic tanycytes are radial glia-like ependymal cells lining the ventrolateral walls and floor of the third ventricle. Recent data show that tanycytes are adult neural stem/progenitor cells, capable of generating neurons that populat…
View article: Mice lacking PC1/3 expression in POMC-expressing cells do not develop obesity
Mice lacking PC1/3 expression in POMC-expressing cells do not develop obesity Open
Pro-opiomelanocortin (POMC) neurons form an integral part of the central melanocortin system regulating food intake and energy expenditure. Genetic and pharmacological studies have revealed that defects in POMC synthesis, processing, and r…
View article: Decreased sensitivity to the anorectic effects of leptin in mice that lack a Pomc-specific neural enhancer
Decreased sensitivity to the anorectic effects of leptin in mice that lack a Pomc-specific neural enhancer Open
Enhancer redundancy has been postulated to provide a buffer for gene expression against genetic and environmental perturbations. While work in Drosophila has identified functionally overlapping enhancers, work in mammalian models has been …
View article: SUN-669 The G209R Mutant Mouse as a Model for Human PCSK1 Polyendocrinopathy
SUN-669 The G209R Mutant Mouse as a Model for Human PCSK1 Polyendocrinopathy Open
A striking number of SNPs and rare mutations have been identified in PCSK1, the gene that codes for the enzyme proprotein convertase 1/3 (PC1/3) which proteolytically activates prohormones within the secretory pathway. All infants bearing …
View article: SAT-299 Chronic Treatment Of Juvenile Hypothalamic Pomc-deficient Mice With RM-493 Prevents The Development Of Obesity
SAT-299 Chronic Treatment Of Juvenile Hypothalamic Pomc-deficient Mice With RM-493 Prevents The Development Of Obesity Open
Arc-Pomc knockout mice have a disruption of the two neural enhancers for the Pomc (proopiomelanocortin) gene, resulting in selective loss of Pomc gene expression in the arcuate nucleus of the hypothalamus. This gene targeting strategy leav…
View article: OR16-03 Metabolic Effects Of Hypothalamic Pomc Neurons Generated Postnatally From Tanycytes On A Pomc Null Genetic Background
OR16-03 Metabolic Effects Of Hypothalamic Pomc Neurons Generated Postnatally From Tanycytes On A Pomc Null Genetic Background Open
Hypothalamic proopiomelanocortin (POMC) neurons are an integral part of the central melanocortin system and regulate feeding and energy balance in vertebrates. Tanycytes are radial glial-like cells lining the third ventricle that contain a…
View article: MON-709 Single-Cell RNA-Sequencing Deciphers POMC Neuron Destiny
MON-709 Single-Cell RNA-Sequencing Deciphers POMC Neuron Destiny Open
The hypothalamus is one of the critical brain nodes regulating body weight and energy homeostasis. Within this node, Pomc neurons sense nutrient and hormonal signals to release melanocortin peptides that induce satiety, whereas AgRP/NPY ne…
View article: Expression of a hypomorphic Pomc allele alters leptin dynamics during late pregnancy
Expression of a hypomorphic Pomc allele alters leptin dynamics during late pregnancy Open
Proopiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus (ARC) are essential for normal energy homeostasis. Maximal ARC Pomc transcription is dependent on neuronal Pomc enhancer 1 (nPE1), located 12 kb upstream from the promo…
View article: The transcriptional regulator PRDM12 is critical for Pomc expression in the mouse hypothalamus and controlling food intake, adiposity, and body weight
The transcriptional regulator PRDM12 is critical for Pomc expression in the mouse hypothalamus and controlling food intake, adiposity, and body weight Open
Altogether, our results demonstrate that PRDM12 plays an essential role in the early establishment of hypothalamic melanocortin neuron identity and the maintenance of high expression levels of Pomc. Its absence in adult mice greatly impair…
View article: Reduced stability and pH-dependent activity of a common obesity-linked PCSK1 polymorphism, N221D
Reduced stability and pH-dependent activity of a common obesity-linked PCSK1 polymorphism, N221D Open
Common mutations in the human prohormone convertase 1/3 (PC1/3) gene (PCSK1) are linked to increased risk of obesity. Previous work has shown that the rs6232 SNP (N221D) results in slightly decreased activity, though whether this decrease …
View article: Nuclear transcriptional changes in hypothalamus of <i>Pomc</i> enhancer knockout mice after excessive alcohol drinking
Nuclear transcriptional changes in hypothalamus of <i>Pomc</i> enhancer knockout mice after excessive alcohol drinking Open
Persistent alterations of proopiomelanocortin ( Pomc ) and mu‐opioid receptor ( Oprm1 ) activity and stress responses after alcohol are critically involved in vulnerability to alcohol dependency. Gene transcriptional regulation altered by …
View article: The Homeodomain Transcription Factor NKX2.1 Is Essential for the Early Specification of Melanocortin Neuron Identity and Activates<i>Pomc</i>Expression in the Developing Hypothalamus
The Homeodomain Transcription Factor NKX2.1 Is Essential for the Early Specification of Melanocortin Neuron Identity and Activates<i>Pomc</i>Expression in the Developing Hypothalamus Open
Food intake is tightly regulated by a group of neurons present in the arcuate nucleus of the hypothalamus, which release Pomc -encoded melanocortins, the absence of which induces marked hyperphagia and early-onset obesity. Although the rel…
View article: Selective Restoration of<i>Pomc</i>Expression in Glutamatergic POMC Neurons: Evidence for a Dynamic Hypothalamic Neurotransmitter Network
Selective Restoration of<i>Pomc</i>Expression in Glutamatergic POMC Neurons: Evidence for a Dynamic Hypothalamic Neurotransmitter Network Open
Hypothalamic POMC deficiency leads to obesity and metabolic deficiencies, largely due to the loss of melanocortin peptides. However, POMC neurons in the arcuate nucleus (ARC) are comprised of glutamatergic and GABAergic subpopulations. The…
View article: NKX2.1 is critical for melanocortin neuron identity, hypothalamic<i>Pomc</i>expression and body weight
NKX2.1 is critical for melanocortin neuron identity, hypothalamic<i>Pomc</i>expression and body weight Open
Food intake is tightly regulated by a group of neurons present in the mediobasal hypothalamus which activate satiety by releasing Pomc -encoded melanocortins. Although the relevance of hypothalamic POMC neurons in the regulation of energy …
View article: Ruboxistaurin Reduces Cocaine-Stimulated Increases in Extracellular Dopamine by Modifying Dopamine-Autoreceptor Activity
Ruboxistaurin Reduces Cocaine-Stimulated Increases in Extracellular Dopamine by Modifying Dopamine-Autoreceptor Activity Open
Cocaine is a highly abused drug, and cocaine addiction affects millions of individuals worldwide. Cocaine blocks normal uptake function at the dopamine transporter (DAT), thus increasing extracellular dopamine. Currently, no chemical thera…