DMD and microlens array as a switchable module for illumination angle scanning in optical diffraction tomography.

Optical diffraction tomography (ODT) enables label-free and morphological 3D imaging of biological samples using refractive-index (RI) contrast. To accomplish this, ODT systems typically capture multiple angular-specific scattering measurements, which are used to computationally reconstruct a sample's 3D RI. Standard ODT systems employ scanning mirrors to generate angular illuminations.

The convergence of mTOR signaling and ethanol teratogenesis.

Ethanol is one of the most common teratogens and causes of human developmental disabilities. Fetal alcohol spectrum disorders (FASD), which describes the wide range of deficits due to prenatal ethanol exposure, are estimated to affect between 1.1 % and 5.

Zebrafish raptor mutation inhibits the activity of mTORC1, inducing craniofacial defects due to autophagy-induced neural crest cell death.

The mechanistic target of rapamycin (mTOR) coordinates metabolism and cell growth with environmental inputs. mTOR forms two functional complexes: mTORC1 and mTORC2. Proper development requires both complexes but mTORC1 has unique roles in numerous cellular processes, including cell growth, survival and autophagy.

Loss of sensitizes embryos to ethanol-induced neural crest and neural apoptosis via generation of reactive oxygen species.

Fetal alcohol spectrum disorders (FASD) are a continuum of birth defects caused by prenatal alcohol exposure. FASD are the most common environmentally induced birth defect and are highly variable. The genetics of an individual influence the severity of their FASD phenotype.

Embryonic ethanol exposure disrupts craniofacial neuromuscular integration in zebrafish larvae.

Forming a vertebrate head involves the meticulous integration of multiple tissue types during development. Prenatal alcohol exposure is known to cause a variety of birth defects, especially to tissues in the vertebrate head. However, a systematic analysis of coordinated defects across tissues in the head is lacking.

Gene-alcohol interactions in birth defects.

Most human birth defects are thought to result from complex interactions between combinations of genetic and environmental factors. This is true even for conditions that, at face value, may appear simple and straightforward, like fetal alcohol spectrum disorders (FASD). FASD describe the full range of structural and neurological disruptions that result from prenatal alcohol exposure.

Predicting Modifiers of Genotype-Phenotype Correlations in Craniofacial Development.

Most human birth defects are phenotypically variable even when they share a common genetic basis. Our understanding of the mechanisms of this variation is limited, but they are thought to be due to complex gene-environment interactions. Loss of the transcription factor Gata3 associates with the highly variable human birth defects HDR syndrome and microsomia, and can lead to disruption of the neural crest-derived facial skeleton.

High-throughput detection of craniofacial defects in fluorescent zebrafish.

Losses and malformations of cranial neural crest cell (cNCC) derivatives are a hallmark of several common brain and face malformations. Nevertheless, the etiology of these cNCC defects remains unknown for many cases, suggesting a complex basis involving interactions between genetic and/or environmental factors. However, the sheer number of possible factors (thousands of genes and hundreds of thousands of toxicants) has hindered identification of specific interactions.

Embryonic Nicotine Exposure Disrupts Adult Social Behavior and Craniofacial Development in Zebrafish.

Cigarette smoking remains the leading cause of preventable death and morbidity worldwide. Smoking during pregnancy is associated with numerous adverse birth outcomes, including craniofacial and behavioral abnormalities. Although tobacco smoke contains more than 4000 toxic substances, nicotine is addictive and is likely the most teratogenic substance in cigarette smoke.

Divergent cis-regulatory evolution underlies the convergent loss of sodium channel expression in electric fish.

South American and African weakly electric fish independently evolved electric organs from muscle. In both groups, a voltage-gated sodium channel gene independently lost expression from muscle and gained it in the electric organ, allowing the channel to become specialized for generating electric signals. It is unknown how this voltage-gated sodium channel gene is targeted to muscle in any vertebrate.

Loss of tumor protein 53 protects against alcohol-induced facial malformations in mice and zebrafish.

Background: Alcohol exposure during the gastrulation stage of development causes the craniofacial and brain malformations that define fetal alcohol syndrome. These malformations, such as a deficient philtrum, are exemplified by a loss of midline tissue and correspond, at least in part, to regionally selective cell death in the embryo. The tumor suppressor protein Tp53 is an important mechanism for cell death, but the role of Tp53 in the consequences of alcohol exposure during the gastrulation stage has yet to be examined.

Exposure to ethanol leads to midfacial hypoplasia in a zebrafish model of FASD via indirect interactions with the Shh pathway.

Background: Gene-environment interactions are likely to underlie most human birth defects. The most common known environmental contributor to birth defects is prenatal alcohol exposure. Fetal alcohol spectrum disorders (FASD) describe the full range of defects that result from prenatal alcohol exposure.

Variation in phenotypes from a Bmp-Gata3 genetic pathway is modulated by Shh signaling.

We sought to understand how perturbation of signaling pathways and their targets generates variable phenotypes. In humans, GATA3 associates with highly variable defects, such as HDR syndrome, microsomia and choanal atresia. We previously characterized a zebrafish point mutation in gata3 with highly variable craniofacial defects to the posterior palate.

Multifactorial Genetic and Environmental Hedgehog Pathway Disruption Sensitizes Embryos to Alcohol-Induced Craniofacial Defects.

Background: Prenatal alcohol exposure (PAE) is perhaps the most common environmental cause of human birth defects. These exposures cause a range of structural and neurological defects, including facial dysmorphologies, collectively known as fetal alcohol spectrum disorders (FASD). While PAE causes FASD, phenotypic outcomes vary widely.

Visible Light Mediated Bidirectional Control over Carbonic Anhydrase Activity in Cells and Using Azobenzenesulfonamides.

Two azobenzenesulfonamide molecules with thermally stable configurations resulting from fluorination of positions to the azo group are reported that can differentially regulate the activity of carbonic anhydrase in the and configurations. These fluorinated probes each use two distinct visible wavelengths (520 and 410 or 460 nm) for isomerization with high photoconversion efficiency. Correspondingly, the isomer of these systems is highly stable and persistent (as evidenced by structural studies in solid and solution state), permitting regulation of metalloenzyme activity without continuous irradiation.

Novel Ethanol-Sensitive Mutants Identified in an F3 Forward Genetic Screen.

Background: Fetal alcohol spectrum disorders (FASD) collectively refer to all deleterious outcomes due to prenatal alcohol exposures. Alterations to the face are common phenotypes in FASD. While alcohol exposure is the underlying cause of FASD, many variables modify the outcomes of such exposures.

Differentially sensitive neuronal subpopulations in the central nervous system and the formation of hindbrain heterotopias in ethanol-exposed zebrafish.

Background: A cardinal feature of prenatal ethanol exposure is CNS damage, resulting in a continuum of neurological and behavioral impairments that are described by the term fetal alcohol spectrum disorders (FASD). FASDs are variable and depend on several factors, including the amount, timing, and duration of prenatal ethanol exposure. To enhance interventions for CNS dysfunction, it is necessary to identify ethanol-sensitive neuronal populations and expand the understanding of factors that modify ethanol teratogenesis.

Social deficits following embryonic ethanol exposure arise in post-larval zebrafish.

Prenatal alcohol exposure is the leading cause of birth defects, collectively termed fetal alcohol spectrum disorders (FASD). In the United States and Canada, 1 in 100 children will be born with FASD. Some of the most commonly debilitating defects of FASD are in social behavior.

Social behavioral phenotyping of the zebrafish casper mutant following embryonic alcohol exposure.

The term Fetal Alcohol Spectrum Disorder (FASD) describes all the deleterious consequences of prenatal alcohol exposure. Impaired social behavior is a common symptom of FASD. The zebrafish has emerged as a powerful model organism with which to examine the effects of embryonic alcohol exposure on social behavior due to an innate strong behavior, called shoaling.

PDGFRA gene, maternal binge drinking and obstructive heart defects.

Obstructive heart defects (OHDs) are a major health concern worldwide. The platelet-derived growth factor (PDGF) genes are known to have regulatory functions that are essential for proper heart development. In a zebrafish model, Pdgfra was further demonstrated to interact with ethanol during craniofacial development.

In vivo zebrafish morphogenesis shows Cyp26b1 promotes tendon condensation and musculoskeletal patterning in the embryonic jaw.

Integrated development of diverse tissues gives rise to a functional, mobile vertebrate musculoskeletal system. However, the genetics and cellular interactions that drive the integration of muscle, tendon, and skeleton are poorly understood. In the vertebrate head, neural crest cells, from which cranial tendons derive, pattern developing muscles just as tendons have been shown to in limb and trunk tissue, yet the mechanisms of this patterning are unknown.

Diving into the world of alcohol teratogenesis: a review of zebrafish models of fetal alcohol spectrum disorder.

The term fetal alcohol spectrum disorder (FASD) refers to the entire suite of deleterious outcomes resulting from embryonic exposure to alcohol. Along with other reviews in this special issue, we provide insight into how animal models, specifically the zebrafish, have informed our understanding of FASD. We first provide a brief introduction to FASD.

Gene-environment interactions in development and disease.

Developmental geneticists continue to make substantial jumps in our understanding of the genetic pathways that regulate development. This understanding stems predominantly from analyses of genetically tractable model organisms developing in laboratory environments. This environment is vastly different from that in which human development occurs.

Fishing for Fetal Alcohol Spectrum Disorders: Zebrafish as a Model for Ethanol Teratogenesis.

Fetal Alcohol Spectrum Disorders (FASD) describes a wide array of ethanol-induced developmental defects, including craniofacial dysmorphology and cognitive impairments. It affects ∼1 in 100 children born in the United States each year. Due to the pleiotropic effects of ethanol, animal models have proven critical in characterizing the mechanisms of ethanol teratogenesis.