Biomedical subjects

Stephen R Price

Publications and source records attributed to Stephen R Price.

5 recordsLinked to original sources

PubMed2006

Type II cadherin ectodomain structures: implications for classical cadherin specificity.

Type I and II classical cadherins help to determine the adhesive specificities of animal cells. Crystal-structure determination of ectodomain regions from three type II cadherins reveals adhesive dimers formed by exchange of N-terminal beta strands between partner extracellular cadherin-1 (EC1) domains. These interfaces have two conserved tryptophan side chains that anchor each swapped strand, compared with one in type I cadherins, and include large hydrophobic regions unique to type II interfaces. The EC1 domains of type I and type II cadherins appear to encode cell adhesive specificity in vitro. Moreover, perturbation of motor neuron segregation with chimeric cadherins depends on EC1 domain identity, suggesting that this region, which includes the structurally defined adhesive interface, encodes type II cadherin functional specificity in vivo.

Amino Acid Sequence↗

PubMed2005

Cadherins and catenins in synapse development.

Cadherin-catenin complexes have been well established as key regulators of cell adhesion. Recent work has elucidated a pivotal role for these molecules in synaptic assembly, remodelling and plasticity. Far from being mere adhesive scaffolds, cadherins might directly regulate cell signalling to modulate synaptic connectivity.

Animals↗

PubMed2004

The generation and diversification of spinal motor neurons: signals and responses.

Motor neurons are probably the best characterised neuronal class in the vertebrate central nervous system and have become a paradigm for understanding the mechanisms that control the development of vertebrate neurons. For many investigators working on this problem the chick embryo is the model system of choice and from these studies a picture of the steps involved in motor neuron generation has begun to emerge. These findings suggest that motor neuron generation is shaped by extracellular signals that regulate intrinsic, cell-autonomous determinants at sequential steps during development. The chick embryo has played a prominent role in identifying the sources of these signals, defining their molecular identities and determining the cell intrinsic programs they regulate.

Animals↗

PubMed2002

ETS gene Pea3 controls the central position and terminal arborization of specific motor neuron pools.

The projection of developing axons to their targets is a crucial step in the assembly of neuronal circuits. In the spinal cord, the differentiation of specific motor neuron pools is associated with the expression of ETS class transcription factors, notably PEA3 and ER81. Their initial expression coincides with the arrival of motor axons in the vicinity of muscle targets and depends on limb-derived signals. We show that in Pea3 mutant mice, the axons of specific motor neuron pools fail to branch normally within their target muscles, and the cell bodies of these motor neurons are mispositioned within the spinal cord. Thus, the induction of an intrinsic program of ETS gene expression by peripheral signals is required to coordinate the central position and terminal arborization of specific sets of spinal motor neurons.

Animals↗

PubMed2002

Regulation of motor neuron pool sorting by differential expression of type II cadherins.

During spinal cord development, motor neurons with common targets and afferent inputs cluster into discrete nuclei, termed motor pools. Motor pools can be delineated by transcription factor expression, but cell surface proteins that distinguish motor pools in a systematic manner have not been identified. We show that the developmentally regulated expression of type II cadherins defines specific motor pools. Expression of one type II cadherin, MN-cadherin, regulates the segregation of motor pools that are normally distinguished by expression of this protein. Type II cadherins are also expressed by proprioceptive sensory neurons, raising the possibility that cadherins regulate additional steps in the development of sensory-motor circuits.

Animals↗