The genesis and functioning of the central nervous system are one of the most intricate and intriguing aspects of embryogenesis. The big lacuna in the field of human CNS development is the lack of accessibility of the human brain for direct observation during embryonic and fetal development. Thus, it is imperative to establish alternative animal models to gain deep mechanistic insights into neurodevelopment, establishment of neural circuitry, and its function. Neurodevelopmental events such as neural specification, differentiation, and generation of neuronal and non-neuronal cell types have been comprehensively studied using a variety of animal models and in vitro model systems derived from human cells. The experimentations on animal models have revealed novel, mechanistic insights into neurogenesis, formation of neural networks, and function. The models, thus serve as indispensable tools to understand the molecular basis of neurodevelopmental disorders (NDDs) arising from aberrations during embryonic development. Here, we review the spectrum of in vivo models such as fruitfly, zebrafish, frog, mice, and nonhuman primates to study neurogenesis and NDDs like microcephaly and Autism Spectrum Disorder. We also discuss nonconventional models such as ascidians and the recent technological advances in the field to study neurogenesis, disease mechanisms, and pathophysiology of human NDDs.
Tetrabutylammonium bromide (TBAB) is a widely used industrial reagent and is commonly found in our aquatic ecosystem as an industrial byproduct. In humans, the ingestion of TBAB causes severe neurological impairments and disorders such as vertigo, hallucinations, and delirium. Yet, the extent of environmental risk and TBAB toxicity to human health is poorly understood. In this study, we aim to determine the developmental toxicity of TBAB using zebrafish embryos as a model and provide novel insights into the mechanism of action of such chemicals on neurodevelopment and the overall embryonic program. Our results show that exposure to TBAB results in impaired development of the brain, inner ear, and pharyngeal skeletal elements in the zebrafish embryo. TBAB treatment resulted in aberrations in the specification of the neural crest precursors, hindbrain segmentation, and otic neurogenesis. TBAB treatment also induced a surge in apoptosis in the head, tail, and trunk regions of the developing embryo. Long-term TBAB exposure resulted in cardiac edema and craniofacial defects. Further, in silico molecular docking analysis indicated that TBAB binds to AMPA receptors and modulates neural developmental genes such as olfactomedin and acetylcholinesterase in the embryonic brain. To summarize, our study highlights the novel effects of TBAB on embryonic brain formation and segmentation, ear morphogenesis, and craniofacial skeletal development.
Embryos and microscopes share a long, remarkable history and biologists have always been intrigued to watch how embryos develop under the microscope. Here we discuss the advances in microscopy which have greatly influenced our current understanding of embryogenesis. We highlight the evolution of microscopes and the optical technologies that have been instrumental in studying various developmental processes. These imaging modalities provide mechanistic insights into the dynamic cellular and molecular events which drive lineage commitment and morphogenetic changes in the developing embryo. We begin the journey with a brief history of microscopy to study embryos.First, we review the principles and optics of light, fluorescence, confocal, and electron microscopy which have been key techniques for imaging cellular and molecular events during embryonic development. Next, we discuss recent key imaging modalities such as light-sheet microscopy, which are suitable for whole embryo imaging. Further, we highlight imaging techniques like multiphoton and super resolution microscopy for beyond light diffraction limit, high resolution imaging. Lastly, we review some of the scattering-based imaging methods and techniques used for imaging human embryos.
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