@article {130, title = {Activity-dependent homeostatic specification of transmitter expression in embryonic neurons.}, journal = {Nature}, volume = {429}, year = {2004}, month = {2004 Jun 3}, pages = {523-30}, abstract = {

Neurotransmitters are essential for interneuronal signalling, and the specification of appropriate transmitters in differentiating neurons has been related to intrinsic neuronal identity and to extrinsic signalling proteins. Here we show that altering the distinct patterns of Ca2+ spike activity spontaneously generated by different classes of embryonic spinal neurons in vivo changes the transmitter that neurons express without affecting the expression of markers of cell identity. Regulation seems to be homeostatic: suppression of activity leads to an increased number of neurons expressing excitatory transmitters and a decreased number of neurons expressing inhibitory transmitters; the reverse occurs when activity is enhanced. The imposition of specific spike frequencies in vitro does not affect labels of cell identity but again specifies the expression of transmitters that are inappropriate for the markers they express, during an early critical period. The results identify a new role of patterned activity in development of the central nervous system.

}, keywords = {Action Potentials, Animals, Calcium, Calcium Signaling, Cell Differentiation, Cells, Cultured, Gene Expression Regulation, Homeostasis, Humans, Neurons, Neurotransmitter Agents, Organ Specificity, Phenotype, Potassium Channels, Inwardly Rectifying, Rats, Sodium Channels, Spinal Cord, Xenopus laevis}, issn = {1476-4687}, doi = {10.1038/nature02518}, author = {Borodinsky, Laura N and Root, Cory M and Cronin, Julia A and Sann, Sharon B and Gu, Xiaonan and Spitzer, Nicholas C} } @article {151, title = {The flexible genome.}, journal = {Nat Rev Genet}, volume = {2}, year = {2001}, month = {2001 May}, pages = {383-7}, abstract = {

A principal assumption underlying contemporary genetic analysis is that the normal function of a gene can be inferred directly from its mutant phenotype. The interactivity among genes that is now being revealed calls this assumption into question and indicates that there might be considerable flexibility in the capacity of the genome to respond to diverse conditions. The reservoir for much of this flexibility resides in the nonspecificity and malleability of gene action.

}, keywords = {Animals, Chromosome Mapping, Genes, Genome, Humans, Phenotype}, issn = {1471-0056}, doi = {10.1038/35072018}, author = {Greenspan, R J} } @article {153, title = {Natural behavior polymorphism due to a cGMP-dependent protein kinase of Drosophila.}, journal = {Science}, volume = {277}, year = {1997}, month = {1997 Aug 8}, pages = {834-6}, abstract = {

Naturally occuring polymorphisms in behavior are difficult to map genetically and thus are refractory to molecular characterization. An exception is the foraging gene (for), a gene that has two naturally occurring variants in Drosophila melanogaster food-search behavior: rover and sitter. Molecular mapping placed for mutations in the dg2 gene, which encodes a cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG). Rovers had higher PKG activity than sitters, and transgenic sitters expressing a dg2 complementary DNA from rover showed transformation of behavior to rover. Thus, PKG levels affected food-search behavior, and natural variation in PKG activity accounted for a behavioral polymorphism.

}, keywords = {Animals, Animals, Genetically Modified, Cyclic GMP, Cyclic GMP-Dependent Protein Kinases, Drosophila melanogaster, Feeding Behavior, Genes, Insect, Larva, Phenotype, Polymorphism, Genetic, Signal Transduction}, issn = {0036-8075}, author = {Osborne, K A and Robichon, A and Burgess, E and Butland, S and Shaw, R A and Coulthard, A and Pereira, H S and Greenspan, R J and Sokolowski, M B} }