Susannah Chang

A FAMILY OF MOLECULES RELATED TO COLLAPSIN IN THE EMBRYONIC CHICK NERVOUS SYSTEM

Signaling molecules with either attractive or repulsive effects on specific growth cones are likely to play a role in guiding axons to their appropriate targets. A chick brain glycoprotein, collapsin, has been shown to be a good candidate for a repulsive guidance cue. We report here the discovery of four new molecules related to collapsin in chick brains. All contain a semaphorin domain. One is structurally very similar to collapsin but is only 50% identical in its amino acid sequence. We have named it collapsin-2. The collapsin-related genes exhibit distinct but overlapping patterns of mRNA expression in the developing spinal cord and the developing visual system. This family of collapsin-related molecules could potentially act as repulsive cues toward specific neuronal populations.

DM-GRASP, a novel immunoglobulin superfamily axonal surface protein that supports neurite extension

We have identified a 95 kd cell surface protein, DM-GRASP, that is expressed on a restricted population of axons. Its expression begins early in chick embryogenesis, and within the spinal cord it is localized to axons in the dorsal funiculus, midline floorplate cells, and motoneurons. Antibodies to DM-GRASP impair neurite extension on axons, and purified DM-GRASP supports neurite extension from chick sensory neurons. We have cloned and sequenced the cDNA corresponding to this protein and find that it is a new member of the immunoglobulin superfamily of adhesion molecules. Consequently we have named this protein DM-GRASP, since it is an immunoglobulin-like restricted axonal surface protein that is expressed in the dorsal funiculus and ventral midline of the chick spinal cord.

Neurofascin: A novel chick cell-surface glycoprotein involved in neurite-neurite interactions

We have identified neurofascin, a novel chick cell-surface glycoprotein involved in neurite-neurite interactions. Neurofascin is defined by its reactivity with monoclonal antibody (MAb) F6, which detects two polypeptides (160 and 185 kd) in immunotransfers of brain plasma membrane proteins. Immunoaffinity chromatography using immobilized MAb F6 yields major molecular mass bands at 185, 160, 135-110, and 92 kd. Fingerprint analyses show that these polypeptides are related. Neurofascin is expressed primarily in fiber-rich areas of embryonic cerebellum, spinal cord, and retina. Fab fragments of polyclonal antibodies to neurofascin interfere with the outgrowth of retinal and sympathetic axons in two different in vitro bioassays. Neurofascin is immunologically distinct from other known neurite-associated surface glycoproteins.

Selective groups of neuronal and mesodermal cells recognized early in grasshopper embryogenesis by a monoclonal antibody

Our aim in generating monoclonal antibodies against the grasshopper nervous system is to identify molecules expressed early in neuronal development. A crude homogenate of the adult nervous system was used as the immunogen, and the hybridoma supernatants were screened on young grasshopper embryos. Here we report on the I-5 monoclonal antibody, which recognizes an antigen appearing in an interesting pattern of ectodermal and mesodermal cells early in the embryonic development of the grasshopper. Amongst the cells stained are the pioneer neurons in the central nervous system and the periphery, and the muscle pioneers.

Grasshopper Growth Cones: Divergent Choices and Labeled Pathways

Publisher Summary The growth cones of individual neurons traverse long distances during embryogenesis, yet they find their correct targets and make their appropriate synaptic connections. One would like to understand how growth cones know where to go (pathway selection) and in particular, how the growth cones of different cells, confronted with the same environment, are determined to make different and stereotyped choices of which way to go. Results demonstrate that growth cones find their correct targets not by random growth, but rather by an active process of precise pathfinding. This chapter shows that the growth cones of pioneer neurons in the central nervous system (CNS) establish stereotyped axonal pathways. The chapter emphasizes the divergent choices made by the growth cones of two sibling pioneer neurons. Later it shows that the growth cones of later cells follow specific axonal pathways laid down by pioneers, and when confronted with several available pathways, make specific choices of which one to follow. The divergent choices made by the growth cones of two sibling interneurons are also emphasized here. Neuronal specificity results in large part from the ability of each individual growth cone to make a sequential series of pathway choices that take it to its correct target. These results lead to propose the “labeled pathways” hypothesis whereby axonal pathways are differentially labeled, probably by cell surface markers, and growth cones use these labels for guidance. One way to search for these “labels” is to make monoclonal antibodies, and progress made using this approach is discussed in this chapter.