Alex L. Kolodkin

The semaphorin genes encode a family of transmembrane and secreted growth cone guidance molecules

In addition to its expression on subsets of axons, grasshopper Semaphorin I (Sema I, previously called Fasciclin [Fas] IV) is expressed on an epithelial stripe in the limb bud, where it functions in the guidance of two sensory growth cones as they abruptly turn upon encountering this sema I boundary. We report here on the cloning and characterization of two sema genes in Drosophila, one in human, and the identification of two related viral sequences, all of which encode proteins with conserved Semaphorin domains. Drosophila sema (D-Sema) I is a transmembrane protein, while D-Sema II and human Sema III are putative secreted proteins that are similar to the recently reported chick collapsin. D-Sema I and D-Sema II are expressed by subsets of neurons and muscles. Genetic analysis in Drosophila reveals that semall is an essential gene that is required for both proper adult behavior and survival.

Sernaphorin III can function as a selective chemorepellent to pattern sensory projections in the spinal cord

Distinct classes of primary sensory neurons in dorsal root ganglia subserve different sensory modalities, terminate in different dorsoventral locations in the spinal cord, and display different neurotrophin response profiles. Large diameter muscle afferents that terminate in the ventral spinal cord are NT-3 responsive, whereas small diameter afferents subserving pain and temperature are NGF responsive and terminate in the dorsal spinal cord. Previous in vitro studies showed that the developing ventral spinal cord secretes a diffusible factor that inhibits the growth of sensory axons. Here we show that this factor repels NGF-responsive axons but has little effect on NT-3-responsive axons. We also provide evidence implicating semaphorin III/collapsin, a diffusible guidance molecule expressed by ventral spinal cord cells, in mediating this effect. These results suggest that semaphorin III functions to pattern sensory projections by selectively repelling axons that normally terminate dorsally.

Unified nomenclature for the semaphorins/collapsins [1]

A new semaphorin is defined as a fully sequenced gene, cDNA, or protein which by sequence homology falls into the semaphorin family of proteins. We have established a Semaphorin Nomenclature web site (http://www.semaphorin-nomenclature.bs.jhmi.edu) that provides details for assigning appropriate names and numbers to new semaphorins, apparent orthologs, gene loci, splice variants, or EST sequences.We recommend that this system of nomenclature be used in all future publications.Semaphorin Nomenclature Committee33441The following scientists have endorsed the use of this nomenclature system: J.A. Bamberg, S. Baumgartner, H. Betz, J. Bolz, A. Chedotal, C.R.L. Christensen, P.M. Comoglio, J.G. Culotti, P. Doherty, H. Drabkin, A. Ensser, M.C. Fishman, B. Fleckenstein, G.J. Freeman, H. Fujisawa, A. Ghosh, D.D. Ginty, C.S. Goodman, S. Guthrie, S. Inagake, R. Keynes, T. Kimura, M. Klagsbrun, A.L. Kolodkin, J.Y. Kuwada, Y. Luo, J.D. Minna, S.L. Naylor, T.P. O’Connor, D.D.M. O’Leary, A. Pini, M.-m. Poo, A.W. Puschel, J.A. Raper, J. Roche, C.J. Shatz, W.D. Snider, E. Soriano, M.K. Spriggs, S.M. Stritmatter, S. Sullivan, L. Tamagnone, M. Tessier-Lavigne, T. Tohyama, J. Verhaagen, F.S. Walsh, and T. Yagi.2Three-letter species designations are based on the first letter of the genus and the first two letters of the species. Additional details about gene nomenclature conventions can be obtained at the Human Gene Nomenclature web site (http://www.gene.ucl.ac.uk/nomenclature/) and the links therein.3The appropriate citation for this letter is: (Semaphorin Nomenclature Committee, 1999).4The committee consists of: please see the list of authors.

Fasciclin IV: Sequence, expression, and function during growth cone guidance in the grasshopper embryo

Monoclonal antibody 6F8 was used to characterize and clone fasciclin IV, a new axonal glycoprotein in the grasshopper, and to study its function during growth cone guidance. Fasciclin IV is dynamically expressed on a subset of axon pathways in the developing CNS and on circumferential bands of epithelial cells in developing limb buds. One of these bands corresponds to the location where the growth cones of the Ti1 pioneer neurons make a characteristic turn while extending toward the CNS. Embryos cultured in the 6F8 antibody or Fab exhibit aberrant formation of this axon pathway. cDNA sequence analysis suggests that fasciclin IV has a signal sequence; long extracellular, transmembrane, and short cytoplasmic domains; and shows no homology with any protein in the available data bases. Thus, fasciclin IV appears to be a novel integral membrane protein that functions in growth cone guidance.

Semaphorin II can function as a selective inhibitor of specific synaptic arborizations

Previous studies showed that grasshopper semaphorin I, a transmembrane semaphorin, functions in vivo to steer a pair of growth cones, prevent defasciculation, and inhibit branching; and that chick collapsin, a secreted semaphorin, can function in vitro to cause growth cone collapse. Semaphorin II, a secreted semaphorin in Drosophila, is transiently expressed by a single large muscle during motoneuron outgrowth and synapse formation. To test the in vivo function of semaphorin II, we created transgenic Drosophila that generate ectopic semaphorin II expression by muscles that normally do not express it. The results show that semaphorin II can function in vivo as a selective target-derived signal that inhibits the formation of specific synaptic terminal arbors.