Retinoid-regulated gene expression in neural development

The discovery and development of information surrounding the retinoic acid receptors (RAR and RXR) has ushered in a new era in understanding the molecular mechanism of action of vitamin A in embryonic development and cellular differentiation. The mechanisms involved in the regulation of gene expression by the retinoids is at least partially known and involves binding of the RAR and RXR to retinoic acid response elements. Additional factors, including coregulatory proteins, associated regulatory elements, and cell-specific factors, may also be involved in determining the specificity of retinoid-regulation of gene expression during development. During embryogenesis, retinoids are required for the development of the posterior hindbrain and its associated structures, as well as for the survival and differentiation of certain classes of neurons and neural crest cell derivatives. At least some of the effects of retinoid on hindbrain development are related to the regulation of Hox gene expression. Additional retinoid-regulated genes have been implicated in nervous system development, and the manner in which they lead to phenotypic changes during embryogenesis remains to be determined.     

Assessing normal embryogenesis in Caenorhabditis elegans using a 4D microscope: variability of development and regional specification

Caenorhabditis elegans is renowned for its invariant embryogenesis. This pattern of development is in apparent contrast to other organisms from Drosophila to higher vertebrates. With the aid of a 4D microscope system (multifocal, time-lapse video recording system) which permits the extensive documentation and analysis of cell divisions, cell positions, and migrations in single embryos we have analyzed normal embryogenesis of C. elegans. The instrumentation reveals a naturally occurring variability in cell division timing, cell positioning, and cell-cell contacts which could not have been detected by the direct observation used earlier (Sulston et al., 1983, Dev. Biol. 100, 64-119). Embryos are very flexible and produce an essentially invariant premorphogenetic stage from variable earlier stages. An analysis of the distribution of the descendants of the early founder blastomeres at the premorphogenetic stage shows that these establish discrete regions in the embryo, a process involving a considerable amount of cell movement, which again varies in different embryos. Only cell fate assignment remains invariant. However, as shown earlier, this is not due to an autonomous invariant specification of cell fates but due to the fact that cell-cell interactions occur very early when the topology of blastomeres in the embryo is still sufficiently precise to ensure reproducible patterns of inductions. A new concept that founder blastomeres produce embryonic regions in the embryo can explain the striking complexity of the lineage per se and also the complicated asymmetric lineage patterns by which the bilateral symmetry of the embryo is established. Many cells, including bilateral homologs, were apparently chosen for a specific fate solely by their position in the embryo, irrespectively of the lineage descent by which the cells are created. We postulate that the production of regions by cell-cell interactions is the pivotal principle guiding the embryogenesis of C. elegans and that the embryogenesis of the worm follows the same basic principles as embryogenesis in other organisms.