A5037798679- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Sexual Differentiation and Disorders
- Neurogenetic and Muscular Disorders Research
- Renal and related cancers
- Animal Genetics and Reproduction
- Amyotrophic Lateral Sclerosis Research
- Signaling Pathways in Disease
- Epigenetics and DNA Methylation
- Alzheimer's disease research and treatments
- Regulation of Appetite and Obesity
- Nerve injury and regeneration
- Cannabis and Cannabinoid Research
- Steroid Chemistry and Biochemistry
- Stress Responses and Cortisol
- Prostate Cancer Treatment and Research
- Parkinson's Disease Mechanisms and Treatments
- Pharmacogenetics and Drug Metabolism
- Congenital heart defects research
- Neuroscience of respiration and sleep
- Neuroendocrine regulation and behavior
- Birth, Development, and Health
- Nuclear Receptors and Signaling
- Cancer-related gene regulation
- Sperm and Testicular Function
- Cholinesterase and Neurodegenerative Diseases
The University of Texas Southwestern Medical Center
2002-2023
Southwestern Medical Center
2002-2018
Nanotherapeutics (United States)
2004-2013
Leptin, an adipocyte-derived hormone, has emerged as a critical regulator of energy homeostasis. The leptin receptor (Lepr) is expressed in discrete regions the brain; among sites highest expression are several mediobasal hypothalamic nuclei known to play role homeostasis, including arcuate nucleus, ventromedial nucleus (VMH), and dorsomedial nucleus. Although most studies have focused on leptin’s actions Lepr these other received less attention. To explore signaling VMH, we used bacterial...
Congenital defects in genital and/or gonadal development occur 1 1000 humans, but the molecular basis for these most cases remains undefined. We show that basic helix-loop-helix transcription factor Pod1(capsulin/epicardin/Tcf21) is essential normal of testes and ovaries, hence sexual differentiation. The gonads Pod1knockout (KO) mice were markedly hypoplastic, urogenital tracts both XX XY remained indistinguishable throughout embryogenesis. Within Pod1 KO gonads, number cells expressing...
The identification of proteins which determine fat and lean body mass composition is critical to better understanding treating human obesity. TDP-43 a well-conserved RNA-binding protein known regulate alternative splicing recently implicated in the pathogenesis amyotrophic lateral sclerosis (ALS). While knockout mice show early embryonic lethality, post-natal conditional weight loss, depletion, rapid death, suggesting an important role for regulating energy metabolism. Here we report, that...
MicroRNA (miRNA) maturation is regulated by interaction of particular miRNA precursors with specific RNA-binding proteins. Following their biogenesis, mature miRNAs are incorporated into the RNA-induced silencing complex (RISC) where they interact mRNAs to negatively regulate protein production. However, little known about how at level activity. To address this, we screened for proteins differentially bound form miR-1 or miR-133 families. These muscle-enriched, co-transcribed pairs cooperate...
The ventromedial hypothalamic nucleus (VMH) plays an important role in the control of feeding and energy homeostasis. In contrast to other nuclei that are also known regulate balance, there is a paucity nucleus-specific marker genes for VMH, limiting application molecular approaches analyzing VMH information processing, function, circuitry. Here, we report use laser-capture microdissection isolate set cDNAs enriched relative two adjacent nuclei, arcuate dorsomedial hypothalamus. expression...
Abstract Knockout (KO) mice lacking the orphan nuclear receptor steroidogenic factor 1 (SF‐1) exhibit marked structural abnormalities of ventromedial nucleus hypothalamus (VMH). In this study, we sought to determine molecular mechanisms underlying VMH abnormalities. To trace SF‐1‐expressing neurons, used a SF‐1/enhanced green fluorescent protein (eGFP) transgene. Although total numbers eGFP‐positive cells in wild‐type (WT) and SF‐1 KO were indistinguishable, that normally localize precisely...
Knockout mice lacking steroidogenic factor 1 (SF-1, officially designated Nr5a1) have a complex phenotype that includes adrenal and gonadal agenesis, impaired expression of pituitary gonadotropins, structural abnormalities the ventromedial hypothalamic nucleus. To explore further how SF-1 regulates endocrine function, we used bacterial artificial chromosome transgenesis to develop lineage marker for SF-1-expressing cells. A genomic fragment containing 50 kb mouse Nr5a1 gene was target...
A variety of transcription factors including Wilms tumor gene (Wt-1), steroidogenic factor 1 (Sf-1), dosage-sensitive sex reversal, adrenal hypoplasia congenita on the X-chromosome, Gene (Dax-1), and pre-B-cell (Pbx1) have been defined as necessary for regular adrenocortical development. However, role Pbx1 growth function in adult organism together with molecular relationship between these other not characterized. We demonstrate that Pbx haploinsufficiency (Pbx1+/−) mice is accompanied by a...
Abstract Background Current treatments for Alzheimer’s disease (AD) have largely failed to yield significant therapeutic benefits. Novel approaches are desperately needed help address this immense public health issue. Data suggests that early intervention at the first stages of mild cognitive impairment may a greater chance success. The calcineurin (CN)-Pin1 signaling cascade can be selectively targeted with tacrolimus (FK506), highly specific, FDA-approved CN inhibitor used safely > 20...
Steroidogenic factor 1 (SF1) is expressed in a time- and cell-specific manner the endocrine system. In this study we present evidence to support that methylation of CpG sites located proximal promoter gene encoding SF1 contributes restricted expression pattern nuclear receptor. DNA analyses revealed nearly perfect correlation between status protein expression, such it was hypomethylated cells express but hypermethylated nonexpressing cells. Moreover, vitro region completely repressed...
The nuclear receptor steroidogenic factor 1 (SF-1) plays essential roles in the development and function of ventromedial hypothalamic nucleus (VMH). Considerable evidence links VMH SF-1 with regulation energy homeostasis. Here, we demonstrate that colocalizes neurons cannabinoid (CB1R) a specific CB1R agonist modulates electrical activity slice preparations. We further show directly regulates gene expression via SF-1-responsive element at -101 its 5'-flanking region. Finally, knockout mice...
Early-stage Alzheimer's disease is characterized by the loss of dendritic spines in neocortex brain. This phenomenon precedes tau pathology, plaque formation, and neurodegeneration likely contributes to synaptic loss, memory impairment, behavioral changes patients. Studies suggest that spine induced soluble, multimeric amyloid-β (Aβ42), which, through postsynaptic signaling, activates protein phosphatase calcineurin. We investigated how calcineurin caused pathology found cis-trans prolyl...
Knockout (KO) mice lacking steroidogenic factor 1 (SF-1, officially designated Nr5a1) have a complex phenotype that includes adrenal and gonadal agenesis, impaired function of pituitary gonadotropes, abnormalities the ventromedial hypothalamic nucleus (VMH). To develop lineage marker for cells express SF-1, we used bacterial artificial chromosome (BAC) transgenesis. A BAC fragment containing 50 kb mouse Nr5a1 gene was placed upstream coding sequence enhanced green fluorescent protein (eGFP)...
The nuclear receptor steroidogenic factor 1 (SF-1 or NR5A1) and the zinc finger protein GATA4 mediate key events in early steps of gonadal development sex differentiation, presumably by activating expression essential target genes. An important SF-1 male differentiation is gene encoding anti-Müllerian hormone (AMH), which induces regression Müllerian ducts developing embryo. In cell transfection studies, there apparent cooperation between regulation both human mouse <i>Amh</i>...
Knockout mice lacking steroidogenic factor 1 (SF-1, officially designated Nr5a1) have a complex phenotype that includes adrenal and gonadal agenesis, impaired expression of pituitary gonadotropins, structural abnormalities the ventromedial hypothalamic nucleus.To explore further how SF-1 regulates endocrine function, we used bacterial artificial chromosome transgenesis to develop lineage marker for SF-1-expressing cells.A genomic fragment containing 50 kb mouse Nr5a1 gene was target enhanced...