Abstract
Advances in labeling technologies are instrumental to study the developmental mechanisms that control organ formation and function at the cellular level. Until recently, genetic tools relied on the expression of single markers to visualize individual cells or lineages in developing and adult animals. Exploiting the expanding color palette of fluorescent proteins and the power of site-specific recombinases in rearranging DNA fragments, the development of Brainbow strategies in mice made it possible to stochastically label many cells in different colors within the same sample. Over the past years, these pioneering approaches have been adapted for other experimental model organisms, including Drosophila melanogaster, zebrafish, and chicken. Balancing the distinct requirements of single cell and clonal analyses, adjustments were made that both enhance and expand the functionality of these tools. Multicolor cell labeling techniques have been successfully applied in studies analyzing the cellular components of neural circuits and other tissues, and the compositions and interactions of lineages. While being continuously refined, Brainbow technologies have thus found a firm place in the genetic toolboxes of developmental and neurobiologists.
Highlights
To address fundamental questions in developmental biology, regardless of the organ, tissue, or model organism, it is essential to visualize cell types of interest
Multicolor cell labeling approaches in vertebrate model organisms rely on the direct transcriptional activation by neuron-specific or ubiquitous enhancers (Table 1)
To achieve tissue or cell-type specificity, Drosophila multicolor labeling techniques tend to control the expression of Brainbow transgenes, whereas tools designed for mice frequently restrict recombinase expression
Summary
One can take advantage of the fact that progeny continue to express the same stable inheritable marker as the precursor, from which they are derived (Figure 1(b)). This may limit anatomical studies if a single reporter is used and cell morphology can no longer be unambiguously determined. This can occur when cells form clusters, are born in the same narrow time window or develop extensive overlapping processes.
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