Nuclear migration: From fungi to the mammalian brain

Textbooks represent the animal cell nucleus as a sort of cellular Jabba the Hutt, torpidly enthroned in the center of the cell. In fact nothing could be farther from the truth. The nucleus more closely resembles Luke Skywalker, the hero of Star Wars, in its ability to move about in its cellular universe. Instances of nuclear motility are found throughout biology. Indeed, nuclear migration appears to be required for the proper growth and development of essentially all eukaryotes. Some well known examples, i.e., those in textbooks, are the congression of male and female pronuclei during fertilization, the movement of nuclei to the egg cortex during embryogenesis in Drosophila melanogaster, and during karyogamy and the migration of the daughter nucleus into the bud in Saccharomyces cerevisiae. Innumerable other nuclear motility events have been described in animals, plants, insects, algae, and fungi. However, until relatively recently, little was known about the mechanism of nuclear migration, except that it required microtubules (MTs)(1). An excellent recent review focuses particularly on how MTs exert forces on nuclei (Reinsch and Gonczy, 1998). The focus of the present review will be on the contribution of genetic systems to our understanding of nuclear migration. The early work on the genetics of nuclear migration came from three "simple" organisms, the yeast S. cerevisiae, and two filamentous fungi, Aspergillus nidulans and Neurospora crassa. Recently, important findings have also come from Drosophila melanogaster, Caenorhabditis elegans, and possibly man. Nuclear migration has been studied in relation to karyogamy and migration of the daughter nucleus into the bud in budding yeast; in relation to the migration of nuclei through the mycelium in the filamentous fungi; during migration to the cortex in fly development; and during cell specific migrations in worm development. Similarities between the NUDF nuclear migration protein of A. nidulans and LIS1, a protein required for neuronal migration in the brain, have led us to suggest that nuclear migration is also a feature of brain development.