A5040389834- Retinoids in leukemia and cellular processes
- Retinal Development and Disorders
- Developmental Biology and Gene Regulation
- Peroxisome Proliferator-Activated Receptors
- Alcohol Consumption and Health Effects
- Antioxidant Activity and Oxidative Stress
- Pancreatic function and diabetes
- Adipose Tissue and Metabolism
- Prenatal Substance Exposure Effects
- Congenital heart defects research
- Neurogenesis and neuroplasticity mechanisms
- Aldose Reductase and Taurine
- Epigenetics and DNA Methylation
- Estrogen and related hormone effects
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Pluripotent Stem Cells Research
- Reproductive System and Pregnancy
- Nuclear Receptors and Signaling
- Pharmacogenetics and Drug Metabolism
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Lipid metabolism and biosynthesis
- Folate and B Vitamins Research
- Eicosanoids and Hypertension Pharmacology
- Nerve injury and regeneration
Sanford Burnham Prebys Medical Discovery Institute
2015-2024
Discovery Institute
2015-2024
Institute for Medical Research
2006-2011
NeuroDevelopment Center
2003
University of Oklahoma Health Sciences Center
2003
Universitat Autònoma de Barcelona
2002
National Foundation for Cancer Research
1992-1996
State University of New York
1996
Cancer Research Center
1994-1995
Cancer Research Foundation
1994
Internal N
Retinoid control of vertebrate development depends upon tissue-specific metabolism retinol to retinoic acid (RA). The RA biosynthetic enzyme RALDH2 catalyzes much, but not all, production in mouse embryos, as revealed here with Raldh2 null mutants carrying an RA-responsive transgene. Targeted disruption arrests at midgestation and eliminates all synthesis except that associated Raldh3 expression the surface ectoderm eye field. Conditional rescue Raldh2–/– embryos by limited maternal...
Genetic studies have shown that retinoic acid (RA) signaling is required for mouse retina development, controlled in part by an RA-generating aldehyde dehydrogenase encoded Aldh1a2 (Raldh2) expressed transiently the optic vesicles. We examined function of a related gene, Aldh1a1 (Raldh1), throughout development dorsal retina. Raldh1(-/-) mice are viable and exhibit apparently normal retinal morphology despite complete absence Raldh1 protein neural RA cup, detected using RARE-lacZ transgene,...
Two isomers of retinoic acid (RA) may be necessary as ligands for retinoid signaling: all-trans-RA RA receptors (RARs) and 9-cis-RA X (RXRs). This was explored by using retinaldehyde dehydrogenase (Raldh)2-/- mouse embryos lacking mesodermal synthesis that display early growth arrest unless rescued administration. Because isomerization to can occur, it is unclear whether both are needed rescue. We show here an RAR-specific ligand rescue Raldh2-/- efficiently all-trans-RA, whereas...
Abstract Studies on nonmammalian vertebrate embryos have indicated that retinoic acid (RA) is required for pancreas development. We analyzed mouse carrying a null mutation of the gene encoding retinaldehyde dehydrogenase 2 ( Raldh2 ), which controls RA synthesis. −/− specifically lack expression Pdx1 (a homeobox development) and Prox1 in dorsal endodermal but not ventral pancreatic precursor tissues. Ventral Hex affected embryos, indicating liver specification dependent upon RA. Also, Foxa2...
Retinoic acid (RA) is required for patterning of the posterior nervous system, but its role in retina remains unclear. RA synthesized discrete regions embryonic eye by three retinaldehyde dehydrogenases(RALDHs) displaying distinct expression patterns. Overlapping functions these enzymes have hampered genetic efforts to elucidate function eye. Here, we report Raldh1, Raldh2 and Raldh3 single,double triple null mice exhibiting progressively less or no synthesis Our studies indicate that...
Retinoic acid (RA) is known to act as a signaling molecule during embryonic development, but little about the regulation of RA synthesis from retinol. The rate-limiting step in oxidation retinol, reaction that can be catalyzed by alcohol dehydrogenase (ADH). Ethanol also substrate for ADH, and high levels ethanol inhibit ADH-catalyzed retinol oxidation. This has prompted us hypothesize ethanol-induced defects observed fetal syndrome involve inhibition synthesis. Here, we have examined effect...
Retinoic acid regulation of one member the human class I alcohol dehydrogenase (ADH) gene family was demonstrated, suggesting that retinol function ADH may play a regulatory role in biosynthetic pathway for retinoic acid. Promoter activity ADH3, but not ADH1 or ADH2, shown to be activated by transient transfection assays Hep3B hepatoma cells. Deletion mapping experiments identified region ADH3 promoter located between -328 and -272 bp which confers activation. This also demonstrated confer...
Abstract Distinct progenitor cell populations exist in cardiac mesoderm important for patterning of the heart. During heart tube formation mouse, Tbx5 is expressed progenitors located more laterally, whereas Isl1 and Fgf8 are medially. Signals that drive mesodermal into various lineages include , which functions to induce . Studies chick zebrafish have shown retinoic acid restricts number progenitors, but its role mammalian development unclear. Here, we demonstrate Raldh2 −/− mouse embryos...
ALDH3A1 (aldehyde dehydrogenase 3A1) is abundant in the mouse cornea but undetectable lens, and ALDH1A1 present at lower (catalytic) levels lens. To test hypothesis that protect anterior segment of eye against environmentally induced oxidative damage, Aldh1a1(-/-)/Aldh3a1(-/-) double knock-out Aldh1a1(-/-) Aldh3a1(-/-) single mice were evaluated for biochemical changes cataract formation (lens opacification). The Aldh1a1/Aldh3a1- Aldh3a1-null develop cataracts posterior subcapsular regions...
In humans and mice, mutations in the Ret gene result Hirschsprung's disease renal defects. embryonic kidney, binding of to its ligand, Gdnf, induces a program epithelial cell remodeling that controls primary branch formation branching morphogenesis within kidney. Our previous studies showed transcription factors belonging retinoic acid (RA) receptor family are crucial for controlling expression ureteric bud; however, mechanism by which retinoid-signaling acts has remained unclear. current...