| Parichy Lab |
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| Overview |
We know a great deal about genetic and cellular mechanisms of early vertebrate development. We know far less about mechanisms underlying adult form and variation in adult form. Nevertheless, identifying the genetic and cellular bases for why adults look the way they do will provide insights into many disease syndromes and birth defects, and is fundamentally important for understanding development and evolution. Towards these ends, research in the lab focuses on several areas including: |
wild-type zebrafish, Danio rerio |
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| We use wild-type and mutant zebrafish as well as closely related species. We also collaborate on studies of salamanders. The lab uses a wide range of techniques, including molecular and classical genetics, in situ hybridization and immunohistochemistry, cell transplantation, light and electron microscopy, time-lapse imaging, cell lineage tracing, transgenesis, and phylogenetic analysis. Lab members are encouraged to integrate multiple approaches into studies of developmental genetics as well as evolution and ecology. We are supported by NIH and NSF. |
| 1. Development and evolution of pigment patterns | |
To better understand the development and evolution of adult form, we use the externally visible pattern formed by pigment cells as a model system. In an evolutionary context, pigment patterns are interesting because they are a complex yet labile trait with clear ecological significance. In a developmental context, pigment patterns are interesting because vertebrate pigment cells are derived from neural crest cells, which also contribute to the craniofacial skeleton, peripheral nervous system, and many other tissues and organs. Thus, we use pigment patterns as a model both for understanding the development and evolution of complex adaptations, and the morphogenesis and differentiation of neural crest derivatives. Current studies aim to identify the genetic and cellular bases for the pigment pattern metamorphosis that transforms an early larval pigment pattern into an adult pigment pattern, as well as the mechanistic bases for pigment pattern variation among species. Areas of particular interest include interactions among pigment cell classes, receptor tyrosine kinase signaling, and contributions of post-embryonic stem cells to pigment pattern variation among species. |
Different species of danios have very different adult pigment patterns, including distinct stripes of black melanophores and orange xanthophores in zebrafish, D. rerio, and more uniform pigment cell arrangements in D. albolineatus. Similar variants are seen in many zebrafish mutants. |
| 2. Post-embryonic neural crest-derived stem cells | |
Understanding vertebrate form requires understanding the neural crest. This is because many of the shared, derived traits of vertebrates have their embryological origins in neural crest cells. In general, development of neural crest cells entails progressive restrictions of fate until terminal differentiation is achieved. Nevertheless, there is now good evidence that some neural crest-derived cells remain undifferentiated as stem cells even into post-embryonic stages. These stem cells are likely to have important roles in the development and maintenance of adult traits, and defects in stem cell populations probably underlie several genetic disease syndromes and cancers. Current studies aim to characterize the stem cell properties of latent, neural crest-derived precursors in zebrafish, and to identify the genes required for establishing and maintaining these cells, as well as recruiting them to particular lineages. Areas of particular interest include roles for neuregulin signals, as well as new genes identified as zebrafish mutants.
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We are testing a model for development of post-embryonic neural crest derivatives derived from latent precursor cells. |
| 3. Dwarfism syndromes and bone development | |
Development of adult form requires coordinated growth and patterning of multiple traits in response to local gene activity as well as global endocrine and physiological mediators. An excellent example of such coordination is the skeleton. Skeletal development affects—and is affected by—growth, and depends on differentiation and morphogenesis of multiple cell types to generate elements with distinct forms and functions throughout the body. In humans, numerous dwarfism syndromes affecting growth and skeletogenesis have been described but only a subset are understood mechanistically. Forward genetics with zebrafish provides an opportunity to identify new models of described growth and skeletal syndromes, as well as new phenotypes and mechanisms. Current studies are focused on trpm7 dwarf mutant zebrafish, and roles for this gene in regulating ossification timing and pattern.
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Clearing and staining for bone and cartilage. |
| 5. Zebrafish behavior and natural history | |
Pigment patterns are some of the most obvious features of animals and often have clear adaptive significance, functioning in camouflage, warning coloration, mate recognition and mate choice. Different danio species exhibit a variety of pigment patterns, as do naturally occurring and induced mutants within zebrafish. To understand the context in which these phenotypes develop, we have undertaken studies of zebrafish natural history and variation in the wild, and we are analyzing the behavioral significance of pigment pattern variation in the laboratory. More information.
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Field sites from our recent survey of zebrafish populations. |
