Seminars in Developmental Biology最新文献

Drosophila is the most genetically malleable animal whichpermits detailed electrophysiological studies. As such, it is an invaluable tool for the genetic dissection of nervous system development and function. In particular, the neuromuscular junction (NMJ) is a large, accessible synapse which can be analysed at all stages of its development. We have been using this synapse to characterize mutations in genes essential to synaptic development and function. These studies suggest that Drosophila synapses develop and function similarly to the synapses of higher animals, using conserved genetic and molecular mechanisms. In the long term, this system will allow us to mutate the genome systematically to identify and describe the genetic and molecular pathways directing the construction of a synapse.

Cadherins comprise a large family of membrane glycoproteins that mediate Ca⁺-dependent cell adhesion during development and in the adult. Although the extracellular domain controls homotypic recognition and binding between cadherins on adjacent cells, proteins that bind to the cytoplasmic domain (catenins) also regulate cell adhesivity. Assembly of the cadherin/catenin complex is temporally and spatially regulated during transport to the cell surface, and in polarized epithelial cells, different cadherin/catenin and catenin complexes have specialized sub-cellular distributions. Changes in the levels of expression, dynamics of assembly and phosphorylation of catenins directly affect cadherin function. Taken together, catenins are emerging as important linkers in cellular processes involved in adhesion, proliferation and morphogenesis.

Integrins are transmembrane receptors for extracellular matrix proteins and cell surface proteins that play important roles in cell adhesion and migration, fibronectin matrix assembly and signal transduction. By inhibiting integrin function through the use of antibodies, antisense RNA and homologous recombination to eliminate genes, integrins have been shown to be vital in both early and late embryogenesis. In early development, β 1 integrins have been shown to play a major role in cell migration during gastrulation and neural crest migration. Later in development, integrins are important in neurite extension and muscle differentiation. Thus, many of the functions attributed to integrins in vitro have also been shown to function during embryogenesis.

The last years have shown that astro- and also oligodendroglia, in addition to supportive properties, may impose restrictions on the pathways of migrating neurons and of extending axonal projections. These inhibitory qualities of central nervous system glia may be important for neural pattern formation. Furthermore, inhibitory properties of glia could play an essential role in the failure of CNS regeneration. The present review discusses the tenascin glycoproteins, extracellular matrix components which belong to a growing family of structurally related genes. Some of these, in particular tenascin and janusin/restrictin, are expressed by glial lineages in the brain and exert both stimulatory and repulsive effects on CNS neurons in vitro.

Traditional views of the role of gap junctions in the vertebrate brain are based on synchronization of neuronal electrical activity through electrotonic coupling. It has become increasingly evident, however, that gap junctions may be more significant as pathways for intracellular second messengers than as passive electrical linkages. Calcium imaging experiments in many non-neuronal cells have demonstrated the presence of propagating, regenerative calcium waves, probably mediated by diffusion of inositol trisphosphate, that appear to play important roles in coordinating the behavior of groups of cells. Expriments in the developing brain indicate that similar mechanisms may be at work, perhaps helping to construct the complex functional assemblies seen in the adult brain.

Many cell adhesion molecules have a distinct pattern of expression and well defined role in cell-cell recognition. By contrast, NCAM is broadly expressed and perturbations of its function affect many diverse aspects of embryonic development. Evidence has been obtained suggesting that the molecule and its unusual polysialic acid moiety serve not only to contribute to specific interactions, but also to regulate overall cell-cell interaction. In this latter mode the molecule can have both a positive and a negative effect on a wide variety of contact-dependent cellular events during development.

A large number of cell adhesion molecules (CAMs) of the immunoglobulin superfamily (IGSF) have been localized to the vertebrate nervous system, and the presence of unique combinations of domains in their molecular structures suggests distinct functions. The presence of many IGSF members on growing axons suggests a role for these molecules in axonal pathfinding and targeting. Nevertheless, the precise nature of that role is only now beginning to unfold. In this review, we will discuss the molecular structure, binding preference and potential signaling capabilities of IGSF CAMs expressed in the nervous system, with emphasis on studies of neurite outgrowth. In addition, the importance of naturally occurring mutations in one of these CAMs, L1, in human brain development will be described.

Interactions of cells with extracellular matrix molecules play a crucial role in development. There is continuous crosstalk between cells and molecules of the extracellular matrix which leads to development of patterns, morphogenesis, differentiation and maintenance of the differentiated phenotype. Many specific receptors for matrix molecules have been identified but we propose here that most processes resulting from matrix-receptor interactions fall into three categories which correspond to different developmental events: (i) cell adhesion/de-adhesion during migration mostly involves interactions via integrin and proteoglycan receptors and their association with cytoskeletal elements; (ii) expression of specific genes during differentiation involves interaction with basement membrane components via integrin recptors and with soluble factors via their receptors; (iii) morphogenesis of epithelial organs, morphogenesis involving cell death, and epithelial-to-mesenchymal transitions involve interactions with ECM that is undergoing remodeling via receptors for enzymes, integrins, proteoglycans and soluble factors