Seminars in Developmental Biology最新文献

Although cleaving vertebrate embryos differ profoundly in shape and size, they all rapidly acquire the same characteristic body pattern during gastrulation. Gastrulating mouse and Xenopus embryos share similar fate maps and gene expression patterns. Furthermore, altering the expression of certain genes and transplantation experiments have comparable consequences, indicating that once underway the molecular mechanisms orchestrating gastrulation may be conserved amongst vertebrates. However, it is less clear that vertebrates necessarily share similar strategies for ensuring the localized induction of mesoderm and hence the initiation of gastrulation.

Secreted polypeptide signalling molecules of the TGF- superfamily play critical roles during mouse development. There are 20 known members of this diverse family in the mouse, including the TGF-s, inhibin/activins, BMPs, GDFs, and nodal. Mutations in genes for some of these ligands have been identified or created by targeted mutagenesis. A complex network of binding proteins, proteases, and receptors is involved in the processing, presentation and biological activity of TGF-β-related ligands. It is likely that variations in these modifying factors will explain how different genetic backgrounds can influence the severity and penetrance of mutant phenotypes.

Mutations introduced into the genes encoding the insulin-like growth factors (IGF) and their receptors indicate that these molecules play critical roles in regulating embryonic growth from mid-gestation onwards. Studies of compound mutations show that IGFI, interacting with the IGF type-1 receptor (IGF1R), has important growth promoting activities in the embryo. Similarly while IGFII signals proliferation via binding to the IGF1R, it also interacts with a second unidentified receptor to ensure normal placental growth. Finally, the growth promoting effects of IGFII during embryogenesis appear to be tightly regulated both by imprinting phenomena associated with the Igf2 locus, and through interactions with the IGF2R/MPR.

Members of the Pax gene family exhibit distinct temporal and spatial expression patterns during murine embryogenesis. Their unique expression in the central nervous system implies a role in the regionalization of the spinal cord and early brain. Pax proteins are localized in the cell nucleus and possess a DNA-binding activity. This makes them good candidates for transcriptional regulator of developmental processes. Mutations in three Pax genes have been associated with three mouse mutants and two human diseases indicating that their activity is necessary for proper development of the embryo

During the early postnatal life of mammals (and analogouslyin other terrestrial vertebrates) the number of motor axons innervating individual muscle fibers undergoes a dramatic change: whereas at birth virtually all muscle fibers are innervated by multiple motor axons, several weeks later every muscle fiber is innervated by one axon. This transition is caused by a competitive interaction between the terminal branches of multiple axons co-innervating the same muscle fiber at the same junction. The muscle fiber seems to be the intermediary in the interaction by selectively initiating changes in the postsynaptic membrane (including loss of AchRs) at the sites occupied by one axon. The postsynaptic changes are soon followed by withdrawal of the overlying nerve terminals. The muscle seems to be able to distinguish the sites occupied by the different axons by virtue of their different activity patterns. These results may help inform on the ways in which experience alters synaptic connections throughout the developing nervous system and in the adult brain.

An intricate series of inductive mechanisms orchestrates the development of synaptic specializations at neuromuscular junctions. We focus our attention on the differentiation of the presynaptic nerve terminal induced by retrograde signals from the muscle cell during the early phase of synaptogenesis. While the molecular signals and mechanisms of induction involved remain largely unknown, ultrastructural, physiological and biochemical studies have begun to define a distinct sequence of cellular events triggered by contact with the target muscle cell.

Inductive interactions between motor neuron and muscle result in the formation of synaptic structures at the neuromuscular junction. The localized appearance of synaptic proteins is due in part to the selective expression of specific genes in the muscle nuclei which lie beneath the motor endplate. For example, synapse-specific expression of the acetylcholine receptor subunit genes contributes to the restricted distribution of the acetylcholine receptor. A transynaptic, motor neuron-derived signal is thought to induce changes in the transcriptional potential of synaptic nuclei. Although the precise mechanisms of gene activation have yet to be elucidated, a neuronally derived factor called ARIA is likely to play a central role in this process.

The neuromuscular junction serves widely as a modelsynapse for both the study of synaptic development and synaptic transmission. We are now attempting to understand the molecular events that underlie these processes. One approach to the study of the neuromuscular junction is to analyse mutants of the nematode Caenorhabditis elegans. We review the motor circuit in the worm responsible for locomotion, the development of the C. elegans neuromuscular junction, and the gene products required for the functioning of nematode synapses. This genetic approach has both identified novel components of the neuromuscular junction and has ascertained the in-vivo roles of biochemically-defined components that regulate neuromuscular transmission and development.

The basal lamina (BL) that ensheaths each skeletal musclefiber passes between the pre- and postsynaptic membranes at the neuromuscular junction. A consequence of this arrangement is that BL comprises much of the synaptic cleft material of this synapse. Some of the cues that guide differentiation and regeneration of both pre- and postsynaptic components are stably associated with synaptic BL. This paper reviews studies aimed at identifying these components and learning how they work.