Alteration of the retinotectal map in Xenopus by antibodies to neural cell adhesion molecules.

Abstract

The neural cell adhesion molecule (N-CAM) mediates neuron-neuron adhesion, is ubiquitous in the nervous system of developing and mature vertebrates, and undergoes major alterations in both amount and distribution during development. Perturbation of homophilic (N-CAM to N-CAM) binding by univalent fragments of specific anti-N-CAM antibodies has previously been found to alter neural tissue patterns in vitro. To show that significant alterations can also occur in vivo, antibodies to Xenopus N-CAM were embedded in agarose microcylinders and implanted in the tecta ofjuvenile Xenopus laevis frogs that were undergoing regeneration of their retinotectai projections; 1 week later, the effects of implantation on the projection pattern from the optic nerve were determined. Both polyclonal and monoclonal antibodies to N2CAM distorted the retinotectal 'projection pattern and greatly decreased the precision of the projection; these alterations recovered to near normal after an additional 3 weeks. Similar but smaller effects were obtained when normally developing froglets received tectal implants. In control animals, implants of immunoglobulins from preimmune serum and monoclonal antibodies not directed against N-CAM had little or no effect on the pattern. The results suggest that neuronal adhesion mediated by N-CAM is important in establishing and maintaining the precision and topography of neural patterns.The neural projection from the eye to the optic tectum (the retinotectal projection) is the major visual pathway in the frog. It is ordered in such a fashion that a "map" of the visual field of the eye is conveyed intact to the contralateral optic tectum. In this map, cells from neighboring regions of the retina send axons down the optic nerve and terminate at neighboring loci in the tectum. The retinotectal system has served as an important model in the analysis of neural patterning because of its stereotyped pattern of connections, its accessibility to experimental intervention, and the availability of straightforward methods for assaying the order of the projection (for a review, see ref. 1). Both the order and the precision of the retinotectal projection can be determined during development and regeneration by means of anatomical or extracellular electrophysiological techniques.After damage to the optic nerve, the retinotectal map can regenerate with proper orientation and near-normal precision within weeks (2-4). While some evidence now indicates that an activity-dependent process is involved in refining the order of the projection, its overall topography can be formed in the absence of visual experience or nerve activity (3, 4). Furthermore, experiments on the development of the projection pattern have indicated that a normally oriented projection can form in the absence of the optic tract or nerve activity (5,6). The overall picture that emerges is that the retinotectal projection is initially patterned by cell interactions independent of the path of arrival of nerve fibers or their neuronal activity; the lat...

Poly (alpha 2,8-deaminoneuraminic acid) is expressed in lung on a single 150-kDa glycoprotein and is an oncodevelopmental antigen.

“…The poly(ca2,8-Neu5Ac) of NCAM modulates the adhesive properties of NCAM and influences other cell adhesion molecules (4)(5)(6)(7)(8). Thereby, it plays a role in the development and differentiation of the nervous system (8)(9)(10)(11) and probably of other organs as indicated by its spatiotemporal expression patterns in fetuses (12). In adults, poly(a2,8-Neu5Ac) becomes restricted to the nervous system and seems to be important in spatial learning and memory formation (13,14).…”

Antibody to a molecular marker of cell position inhibits synapse formation in retina.

“…In the present study, the role of molecular markers of cell position in the development of the nervous system was examined by using a monoclonal antibody to TOP. Antibodies provide a means of blocking molecular function (4-7), and antibodies to neuronal surface molecules have been used to disturb growth cone behavior and disrupt neurite outgrowth (8)(9)(10)(11)(12)(13)(14).Our objectives were to determine the accessibility of TOP in the in vivo retina to antibody, to determine the persistence of antibody in the retina after injection into the embryo, and to identify changes in the development of retina that is continuously exposed to anti-TOP antibody. Antibody injected extraembryonically into the amniotic cavity of young embryos in ovo and injected intraocularly into older embryos diffused into the retina and formed [antibody-TOP] ([Ab-TOP]) complexes in the expected gradient.…”

“…In the present study, the role of molecular markers of cell position in the development of the nervous system was examined by using a monoclonal antibody to TOP. Antibodies provide a means of blocking molecular function (4)(5)(6)(7), and antibodies to neuronal surface molecules have been used to disturb growth cone behavior and disrupt neurite outgrowth (8)(9)(10)(11)(12)(13)(14).…”

Transcription initiation sites and structural organization of the extreme 5' region of the rat neural cell adhesion molecule gene.

“…This binding has been shown to mediate cell-to-cell and cell-to-extracellular matrix adhesion (37,52,53). NCAMmediated adhesion appears to play a central role in various morphogenetic processes, including neural crest migration (59), orderly outgrowth of axons (5), cell patterning and tissue formation (10), and nerve-muscle interaction (20).…”