Biomedical subjects

Robert J Wyman

Publications and source records attributed to Robert J Wyman.

4 recordsLinked to original sources

PubMed2005

Experimental analysis of nature-nurture interactions.

The presumed opposition of nature and nurture has been a major concern of western civilization since its beginnings. Christian theologians interpreted Adam and Eve's eating of the forbidden fruit as the origin of an inherited 'original sin'. Saint Augustine explicitly applied the concept to human mental development, arguing that, because of original sin, children are inclined toward evil and education requires physical punishment. For centuries, it was considered parents' moral and religious obligation, not to nurture their children, in our current sense of that word, but to beat the willfulness out of them. 16thC humanists fought back, arguing that "schools have become torture chambers" while it is adults "who corrupt young minds with evil". Locke's (1690) statement that children are born as a 'white paper' was crucial in rejecting the dogma of an inborn (and sinful) nature. The original sin vs. white paper argument merged with another ancient dichotomy: inborn instinct (which controls animal behavior) vs. the reason and free will which humans have. Darwin made the concept of inherited instinct, common to both man and animals, one cornerstone of his theory of evolution. The 20(th)C saw scientists recast the debate as instinct vs. learning, bitterly argued between behaviorists and ethologists. Laboratory experimentation and field observation showed that behavior could develop without learning but also that conditioning paradigms could powerfully mold behavior. The progress of genetics and neurobiology has led to the modern synthesis that neural development, and hence behavior, results from the interdependent action of both heredity and environment.

Acculturation↗

PubMed2005

Basigin (EMMPRIN/CD147) interacts with integrin to affect cellular architecture.

Basigin, an IgG family glycoprotein found on the surface of human metastatic tumors, stimulates fibroblasts to secrete matrix metalloproteases that remodel the extracellular matrix. Using Drosophila melanogaster we identify intracellular, matrix metalloprotease-independent, roles for basigin. Specifically, we found that basigin, interacting with integrin, is required for normal cell architecture in some cell types. Basigin promotes cytoskeletal rearrangements and the formation of lamellipodia in cultured insect cells. Loss of basigin from photoreceptors leads to misplaced nuclei, rough ER and mitochondria, as well as to swollen axon terminals. These changes in intracellular structure suggest cytoskeletal disruptions. These defects can be rescued by either fly or mouse basigin. Basigin and integrin colocalize to cultured cells and to the visual system. Basigin-mediated changes in the architecture of cultured cells require integrin binding activity. Basigin and integrin interact genetically to affect cell structure in the animal, possibly by forming complexes at cell contacts that help organize internal cell structure.

Actins↗

PubMed2002

Gap junction proteins are not interchangeable in development of neural function in the Drosophila visual system.

Gap junctions (GJs) are composed of proteins from two distinct families. In vertebrates, GJs are composed of connexins; a connexin hexamer on one cell lines up with a hexamer on an apposing cell to form the intercellular channel. In invertebrates, GJs are composed of an unrelated protein family, the innexins. Different connexins have distinct properties that make them largely non-interchangeable in the animal. Innexins are also a large family with high sequence homology, and some functional differences have been reported. The biological implication of innexin differences, such as their ability to substitute for one another in the animal, has not been explored. Recently, we showed that GJ proteins are necessary for the development of normal neural transmission in the Drosophila visual system. Mutations in either of two Drosophila GJ genes (innexins), shakB and ogre, lead to a loss of transients in the electroretinogram (ERG), which is indicative of a failure of the lamina to respond to retinal cell depolarization. Ogre is required presynaptically and shakB(N) postsynaptically. Both act during development. Here we ask if innexins are interchangeable in their role of promoting normal neural development in flies. Specifically, we tested several innexins for their ability to rescue shakB(2) and ogre mutant ERGs and found that, by and large, innexins are not interchangeable. We mapped the protein regions required for this specificity by making molecular chimeras between shakB(N) and ogre and testing their ability to rescue both mutants. Each chimera rescued either shakB or ogre but never both. Sequences in the first half of each protein are necessary for functional specificity. Potentially crucial residues include a small number in the intracellular loop as well as a short stretch just N-terminal to the second transmembrane domain. Temporary GJs, possibly between the retina and lamina, may play a role in final target selection and/or chemical synapse formation in the Drosophila visual system. In that case, specificity in GJ formation or function could contribute, directly or indirectly, to chemical synaptic specificity by regulating which neurons couple and what signals they exchange. Cells may couple only if their innexins can mate with each other. The partially overlapping expression patterns of several innexins make this 'mix and match' model of GJ formation a possibility.

Amino Acid Sequence↗

PubMed2002

Gap junction proteins expressed during development are required for adult neural function in the Drosophila optic lamina.

We provide evidence that gap junction proteins, expressed during development, are necessary for the formation of normally functioning connections in the Drosophila optic lamina. Flies with mutations in the gap junction genes (innexins), shakingB, and ogre have normal photoreceptor potentials but a defective response of the postsynaptic cells in the optic lamina. This is indicated by a reduction in, or absence of, transients in the electroretinogram. Ogre is required in the presynaptic retinal photoreceptors. ShakingB(N) is, at a minimum, required in postsynaptic lamina neurons. Transgenic expression of the appropriate innexins during pupal development (but not later) rescues connection defects. Transient gap junctions have been observed to precede chemical synapse formation and have been hypothesized to play a role in connectivity and synaptogenesis; however, no causal role has been demonstrated. Here we show that developmental gap junction genes can be required for normally functioning neural connections to form.

Animals↗