Key Points
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This article briefly discusses the role of experimental embryology (and experimental embryologists) in discovering the principles of vertebrate neural development. It provides a historical account of the roles of cutting, pasting and painting, as well as modifications of these techniques that have led to new approaches, in elucidating the principles of neural development.
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Experimental embryologists have mainly used four vertebrate models to work out the principles of neural development: amphibians, chicks, mice and zebrafish. The strengths and weaknesses of these four vertebrate models are discussed.
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Experimental embryology is founded on three main techniques. 'Cutting' involves either ablation — the removal and discarding of a tissue, a group of cells or single cells to test whether they are required for a particular developmental event — or the isolation of tissues and cells for further testing. 'Pasting' involves transplanting tissues or cells from donor to host embryos. 'Painting' involves the use of labelled cells for the purpose of tracking cell movements and fates during further development.
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The central principle of vertebrate neural development is that the nervous system and associated structures, such as the nose, eyes, ears and (in some organisms) lateral line, arise through a series of inductive interactions between neighbouring cells. The use of cutting, pasting and painting by experimental embryologists has revealed several key principles of neural development that are related to the central principle.
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The techniques of experimental embryology have contributed to the elucidation of a number of principles of vertebrate neural development. This review outlines the crucial series of experiments that led to the discovery of neural induction, and recent modifications of experimental embryological techniques that have been used to begin to work out its molecular mechanisms.
Abstract
The goal of experimental embryology seems rather simple: to manipulate embryos in systematic ways to elucidate mechanisms of development. Such manipulation involves variations in three main techniques — cutting, pasting and painting — and all three techniques have contributed enormously to the establishment of key principles of neural development.
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Acknowledgements
Research on this subject in my laboratory was supported by the US National Institutes of Health. This article is dedicated to the memory of Viktor Hamburger, a pioneer in experimental embryology and neural development, and one of my scientific heroes. I am indebted to the late R. M. Sweeney, L. Vakaet and R. L. Watterson for teaching me the elegance of avian experimental embryology. I thank J.-F. Colas and R. Ladher for their critical comments on drafts of this manuscript. I apologize to those many authors whose work could not be considered here owing to space constraints; rather than being exhaustive, cited references merely provide examples of relevant studies.
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Glossary
- DOMINANT NEGATIVE
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A mutant molecule capable of forming a heteromeric complex with the normal molecule, knocking out the activity of the entire complex.
- FORWARD-GENETIC SCREEN
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A genetic analysis that proceeds from phenotype to genotype by positional cloning or candidate-gene analysis.
- ELECTROPORATION
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The transient generation of pores in a cell membrane by exposing the cell to a high field strength electrical pulse.
- IONTOPHORESIS
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The introduction of a substance into a cell by ion transfer, using electrodes to apply an electrical potential to the membrane.
- CRE/LOXP
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A site-specific recombination system derived from Escherichia coli bacteriophage P1. Two short DNA sequences (loxP sites) are engineered to flank the target DNA. Activation of the Cre-recombinase enzyme catalyses recombination between the loxP sites, leading to excision of the intervening sequence.
- MORPHOLINO
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An antisense oligonucleotide that acts specifically to block the initiation of translation.
- GASTRULATION
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The process by which the embryo becomes regionalized into three layers: ectoderm, mesoderm and endoderm.
- NEURULATION
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A morphogenetic process during which the progenitors of the nervous system segregate from the ectoderm as a dorsal, hollow nerve cord.
- NOTOCHORD
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A rod-like structure of mesodermal origin that is found in vertebrate embryos. It participates in the differentiation of the ventral neural tube and in the specification of motor neurons.
- FLOOR PLATE
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The ventral cells of the neural tube that lie in the midline.
- ISTHMUS
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A narrow section of the neural tube, which separates the midbrain from the hindbrain.
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Schoenwolf, G. Cutting, pasting and painting: experimental embryology and neural development. Nat Rev Neurosci 2, 763–771 (2001). https://doi.org/10.1038/35097549
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DOI: https://doi.org/10.1038/35097549
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