A5076450562- Growth Hormone and Insulin-like Growth Factors
- Effects and risks of endocrine disrupting chemicals
- Hypothalamic control of reproductive hormones
- Pluripotent Stem Cells Research
- Congenital heart defects research
- Neuroscience and Neuropharmacology Research
- Neuroendocrine regulation and behavior
- Animal Genetics and Reproduction
- Developmental Biology and Gene Regulation
- Pituitary Gland Disorders and Treatments
- Regulation of Appetite and Obesity
- Genetic Syndromes and Imprinting
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Reproductive System and Pregnancy
- Toxic Organic Pollutants Impact
- Neonatal Respiratory Health Research
- Pediatric Hepatobiliary Diseases and Treatments
- Chemical Analysis and Environmental Impact
- Hedgehog Signaling Pathway Studies
- Ovarian function and disorders
- Renal and related cancers
- Pancreatic function and diabetes
- Estrogen and related hormone effects
- Pharmacological Effects and Toxicity Studies
- Cancer-related Molecular Pathways
University of Illinois Urbana-Champaign
2015-2024
University of Illinois System
2007-2020
Center for Genomic Science
2008
University of Michigan
2002-2007
University of California System
2002
Saitama University
2002
Nanoprobes (United States)
2002
Gunma University
2002
Tokushima University
2002
Ventana Research Corporation (United States)
2002
Abstract Mutations in the PROP1 transcription factor gene lead to reduced production of thyrotropin, GH, prolactin, and gonadotropins as well pituitary hypoplasia adult humans mice. Some PROP1-deficient patients initially exhibit hyperplasia that resolves hypoplasia. To understand this feature explore mechanism whereby regulates anterior gland growth, we carried out longitudinal studies normal Prop1-deficient dwarf mice from early embryogenesis through adulthood, examining volume Rathke’s...
Deficiencies in the homeobox transcription factors LHX4 and PROP1 cause pituitary hormone deficiency both humans mice. Lhx4 Prop1 mutants exhibit severe anterior hypoplasia resulting from limited differentiation expansion of most specialized cell types. Little is known about mechanism through which these genes promote development. In this study we determined that results increased death reduced attributable to a temporal shift Lhx3 activation. contrast, normal proliferation survival but show...
During testis development, fetal Leydig cells increase their population from a pool of progenitor rather than proliferation differentiated cell population. However, the mechanism that regulates stem self-renewal and differentiation is unknown. Here, we show blocking Notch signaling, by inhibiting gamma-secretase activity or deleting downstream target gene Hairy/Enhancer-of-split 1, results in an testis. By contrast, constitutively active signaling gonadal somatic causes dramatic loss,...
Neuregulin (NRG), a growth and differentiation factor that signals via erbB receptor tyrosine kinases, has been shown to have biological effects in both the CNS peripheral nervous system. We report here erbB4 is expressed mature cerebellar granule cells, where it appears be concentrated at cell postsynaptic terminals. also show one form of NRG, Ig-NRG, plays crucial role aspects development vitro . First, Ig-NRG treatment cells culture selectively induces expression GABA A β2 subunit. This...
Mutations in Prophet of PIT1 (Prop1), one several homeodomain transcription factors that are required for the development anterior pituitary gland, predominant cause MPHD (multiple hormone deficiency) humans. We show deletion Prop1 mice causes severe hypoplasia with failure entire Pit1 lineage and delayed gonadotrope development. The deficiencies secondary endocrine problems a high rate perinatal mortality due to respiratory distress. Lung atelectasis mutants correlates reduced levels NKX2.1...
Mutations in the transcription factors PIT1 (pituitary factor 1) and PROP1 (prophet of Pit1) lead to pituitary hormone deficiency hypopituitarism mice humans. To determine basis for this, we performed histological analysis Pit1- Prop1-deficient dwarf mouse pituitaries throughout fetal postnatal development. Pit1-deficient first exhibit hypoplasia after birth, primarily caused by reduced cell proliferation, although there is some apoptosis. whether altered development vascular system...
The pituitary is an endocrine gland responsible for the release of hormones, which regulate growth, metabolism, and reproduction. Diseases such as hypopituitarism or adenomas are able to disrupt function leading suboptimal entire system. Growth during development adulthood a tightly regulated process. Hairy enhancer split (HES1), transcription factor whose expression initiated by Notch signaling pathway, repressor cell cycle inhibitors. We hypothesize that with loss Hes1, progenitors no...
Mutations in PROP1 account for up to half of the cases combined pituitary hormone deficiency that result from known causes. Despite this, few signaling molecules and pathways influence expression have been identified. Notch has linked Prop1 expression, but developmental periods during which influences overall development remain unclear. To test requirement establishing normal milieu, we generated mice with early embryonic conditional loss Notch2 (conditional knockout) examined consequences...
The pituitary gland is composed of hormone-producing cells essential for homeostasis and reproduction. Pituitary are sensitive to endocrine feedback in the adult can have altered hormonal secretion from exposure disruptor bisphenol A (BPA). BPA a prevalent plasticizer used food beverage containers, leading widespread human exposure. Although prenatal impact reproductive function adult, effects on developing unknown. We hypothesized that low doses impacts gonadotroph cell number or parameters...
Abstract Background Congenital hypopituitarism (CH) and its associated syndromes, septo-optic dysplasia (SOD) holoprosencephaly (HPE), are midline defects that cause significant morbidity for affected people. Variants in 67 genes with CH, but a vast majority of CH cases lack genetic diagnosis. Whole exome whole genome sequencing patients identifies sequence variants known to new candidate genes, many these uncertain significance (VUS). Methods The International Mouse Phenotyping Consortium...
Abstract Normal pituitary gland development requires coordination between maintenance of progenitor cell pools and selection progenitors for differentiation. The spatial temporal expression Notch2 during suggested that it could control differentiation in the pituitary. Consistent with this idea, is not expressed Prop1 mutants, anterior mutants appear to be unable transition from proliferation properly, resulting lobe failed specification evolving hypoplasia. To test function directly, we...
The hypothalamic arcuate nucleus (Arc), containing pro-opoiomelanocortin (POMC), neuropeptide Y (NPY) and growth hormone releasing (GHRH) neurons, regulates feeding, energy balance body size. Dysregulation of this homeostatic mediator underlies diseases ranging from failure to obesity. Despite considerable investigation regarding the function Arc mechanisms governing their development remain unclear. Notch signaling factors such as Hes1 Mash1 are present in progenitors that give rise...
The progenitor cells of the developing liver can differentiate toward both hepatocyte and biliary cell fates. In addition to established roles TGFβ Notch signaling in this fate specification process, there is increasing evidence that progenitors are sensitive mechanical cues. Here, we utilized microarrayed patterns provide a controlled biochemical biomechanical microenvironment for mouse differentiation. these defined circular geometries, observed differentiation at periphery hepatocytic...
Domesticated species exhibit a suite of behavioral, endocrinological, and morphological changes referred to as "domestication syndrome." These may include reduction in reactivity the hypothalamic-pituitary-adrenal (HPA) axis specifically reduced adrenocorticotropic hormone release from anterior pituitary. To investigate biological mechanisms targeted during domestication, we investigated gene expression pituitaries experimentally domesticated foxes (Vulpes vulpes). RNA was sequenced...
Abstract Di(2-ethylhexyl) phthalate and diisononyl are widely used as plasticizers in polyvinyl chloride products. Short-term exposures to phthalates affect hormone levels, ovarian follicle populations, gene expression. However, limited data exist regarding the effects of long-term exposure on reproductive functions. Thus, this study tested hypothesis that short-term di(2-ethylhexyl) or disrupts dynamics, pituitary expression, levels female mice. Adult CD-1 mice were exposed vehicle,...
Abstract The GABA A receptor β subunit is required to confer sensitivity γ‐aminobutyric acid (GABA), the major inhibitory neurotransmitter in CNS. In previous studies we demonstrated that growth and differentiation factor neuregulin 1 (NRG1) selectively induced expression of β2 mRNA encoded protein rat cerebellar granule neurons culture. present report examine signaling pathways mediate this effect. These demonstrate effects NRG1 on polypeptide require activation ErbB4 tyrosine kinase; its...