RESUMEN
Our understanding of the neural crest, a key vertebrate innovation, is built upon studies of multiple model organisms. Early research on neural crest cells (NCCs) was dominated by analyses of accessible amphibian and avian embryos, with mouse genetics providing complementary insights in more recent years. The zebrafish model is a relative newcomer to the field, yet it offers unparalleled advantages for the study of NCCs. Specifically, zebrafish provide powerful genetic and transgenic tools, coupled with rapidly developing transparent embryos that are ideal for high-resolution real-time imaging of the dynamic process of neural crest development. While the broad principles of neural crest development are largely conserved across vertebrate species, there are critical differences in anatomy, morphogenesis, and genetics that must be considered before information from one model is extrapolated to another. Here, our goal is to provide the reader with a helpful primer specific to neural crest development in the zebrafish model. We focus largely on the earliest events-specification, delamination, and migration-discussing what is known about zebrafish NCC development and how it differs from NCC development in non-teleost species, as well as highlighting current gaps in knowledge.
Asunto(s)
Cresta Neural/embriología , Cresta Neural/metabolismo , Pez Cebra/embriología , Pez Cebra/metabolismo , Animales , Movimiento Celular/genética , Movimiento Celular/fisiología , Transición Epitelial-Mesenquimal/genética , Transición Epitelial-Mesenquimal/fisiología , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismoRESUMEN
The neural crest-a key innovation of the vertebrates-gives rise to diverse cell types including melanocytes, neurons and glia of the peripheral nervous system, and chondrocytes of the jaw and skull. Proper development of the cephalic region is dependent on the tightly-regulated specification and migration of cranial neural crest cells (NCCs). The core PCP proteins Frizzled and Disheveled have previously been implicated in NCC migration. Here we investigate the functions of the core PCP proteins Prickle1a and Prickle1b in zebrafish cranial NCC development. Using analysis of pk1a and pk1b mutant embryos, we uncover similar roles for both genes in facilitating cranial NCC migration. Disruption of either gene causes pre-migratory NCCs to cluster together at the dorsal aspect of the neural tube, where they adopt aberrant polarity and movement. Critically, in investigating Pk1-deficient cells that fail to migrate ventrolaterally, we have also uncovered roles for pk1a and pk1b in the epithelial-to-mesenchymal transition (EMT) of pre-migratory NCCs that precedes their collective migration to the periphery. Normally, during EMT, pre-migratory NCCs transition from a neuroepithelial to a bleb-based and subsequently, mesenchymal morphology capable of directed migration. When either Pk1a or Pk1b is disrupted, NCCs continue to perform blebbing behaviors characteristic of pre-migratory cells over extended time periods, indicating a block in a key transition during EMT. Although some Pk1-deficient NCCs transition successfully to mesenchymal, migratory morphologies, they fail to separate from neighboring NCCs. Additionally, Pk1b-deficient NCCs show elevated levels of E-Cadherin and reduced levels of N-Cadherin, suggesting that Prickle1 molecules regulate Cadherin levels to ensure the completion of EMT and the commencement of cranial NCC migration. We conclude that Pk1 plays crucial roles in cranial NCCs both during EMT and migration. These roles are dependent on the regulation of E-Cad and N-Cad.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Movimiento Celular/fisiología , Transición Epitelial-Mesenquimal/fisiología , Proteínas con Dominio LIM/metabolismo , Cresta Neural/embriología , Proteínas de Pez Cebra/metabolismo , Pez Cebra/embriología , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Cadherinas/genética , Cadherinas/metabolismo , Técnicas de Silenciamiento del Gen , Proteínas con Dominio LIM/genética , Cresta Neural/citología , Tubo Neural/citología , Tubo Neural/embriología , Pez Cebra/genética , Proteínas de Pez Cebra/genéticaRESUMEN
Neural crest cells are multipotent progenitors that dynamically interpret diverse microenvironments to migrate significant distances as a loosely associated collective and contribute to many tissues in the developing vertebrate embryo. Uncovering details of neural crest migration has helped to inform a general understanding of collective cell migration, including that which occurs during cancer metastasis. Here, we discuss several commonalities and differences of neural crest and cancer cell migration and behavior. First, we focus on some of the molecular pathways required for the initial specification and potency of neural crest cells and the roles of many of these pathways in cancer progression. We also describe epithelial-to-mesenchymal transition, which plays a critical role in initiating both neural crest migration and cancer metastasis. Finally, we evaluate studies that demonstrate myriad forms of cell-cell and cell-environment communication during neural crest and cancer collective migration to highlight the remarkable similarities in their molecular and cell biological regulation.