Assessing teratogenic changes in a zebrafish model of fetal alcohol exposure.

Fetal alcohol syndrome (FAS) is a severe manifestation of embryonic exposure to ethanol. It presents with characteristic defects to the face and organs, including mental retardation due to disordered and damaged brain development. Fetal alcohol spectrum disorder (FASD) is a term used to cover a continuum of birth defects that occur due to maternal alcohol consumption, and occurs in approximately 4% of children born in the United States.

Requirement of Npc1 and availability of cholesterol for early embryonic cell movements in zebrafish.

Niemann-Pick disease, type C (NP-C), often associated with Niemann-Pick disease, type C1 (NPC1) mutations, is a cholesterol-storage disorder characterized by cellular lipid accumulation, neurodegeneration, and reduced steroid production. To study NPC1 function in vivo, we cloned zebrafish npc1 and analyzed its gene expression and activity by reducing Npc1 protein with morpholino (MO)-oligonucleotides. Filipin staining in npc1-morphant cells was punctate, suggesting abnormal accumulation of cholesterol.

Visualization of Gli activity in craniofacial tissues of hedgehog-pathway reporter transgenic zebrafish.

Background: The Hedgehog (Hh)-signaling pathway plays a crucial role in the development and maintenance of multiple vertebrate and invertebrate organ systems. Gli transcription factors are regulated by Hh-signaling and act as downstream effectors of the pathway to activate Hh-target genes. Understanding the requirements for Hh-signaling in organisms can be gained by assessing Gli activity in a spatial and temporal fashion.

Deciphering the role of Shh signaling in axial defects produced by ethanol exposure.

Background: The phenotype of embryos exposed to ethanol is complex and likely due to multiple alterations in developmental pathways. We have previously demonstrated that Sonic hedgehog signaling (Shh-s) was reduced in both chicken and zebrafish embryos when exposed to ethanol.

Methods: There are many tissues affected by embryonic ethanol exposure, and in this article we explore the development of axial tissues, using zebrafish embryos.

Molecular changes associated with teratogen-induced cyclopia.

Background: Exposure of zebrafish embryos to a number of teratogens results in cyclopia, but little is known about the underlying molecular changes.

Methods: Using zebrafish embryos, we compare the effects cyclopamine, forskolin, and ethanol delivered starting just before gastrulation, on gene expression in early axial tissues and forebrain development.

Results: Although all three teratogens suppress gli1 expression, they do so with variable kinetics, suggesting that while suppression of Shh signaling is a common outcome of these three teratogens, it is not a common cause of the cyclopia.

Ethanol effects on the developing zebrafish: neurobehavior and skeletal morphogenesis.

Exposure to ethanol during development can lead to a constellation of congenital anomalies, resulting in prenatal and postnatal failure to thrive, central nervous system (CNS) deficits, and a number of patterning defects that lead to defects in the cardiovascular system, facial structures, and limbs. The cellular, biochemical, and molecular mechanisms by which ethanol exerts its developmental toxicity and the genes that influence sensitivity to developmental ethanol exposure have yet to be discovered, despite being one of the more common nongenetic causes of birth defects. The zebrafish undergoes much the same patterning and morphogenesis as other vertebrate embryos do--including humans--that are distinct and cannot be studied in invertebrates.

Strain-dependent effects of developmental ethanol exposure in zebrafish.

Developmental ethanol exposure from maternal consumption of alcoholic beverages and many other consumer products has been linked to developmental abnormalities in humans and animal models. The sensitivity of an individual to ethanol-induced perturbation of developmental processes is strongly influenced by genetic factors. In this study, we show that there are strain- and dose-dependent differences in sensitivity to developmental ethanol exposure in zebrafish (Danio rerio), suggesting that genetic variation within regulatory factors, influencing critical developmental pathways, is responsible for these differences.