Studies on neurotrophic and substrate — attached neurite outgrowth factors

STUDIES ON NEUROTROPHIC AND SUBSTRATE - ATTACHED NEURITE OUTGROWTH FACTORS Reichardt, L.F . , Calof, A.L., Gorin, P .D., Greenspan, R.J., Greif, K. F., 1,ander, A.D. Matthew, W.D., Shelton, D.L., Tomaselli, K., & Winter, J. Dept. Physiology, UCSF, San Francisco, CA 94143 Neurons require appropriate substrata on vhich to extend neurltes and the composltion of the substrata encountered in vivo is believed to regulate both. the extent and directlon of axon growth as well as t he position at which synaptic speciallzations appear. In particular, three constituents of extracellular matrix--fib r onectin, laminin, and factors associated with heparan sulfate proteo- glycans--have dr amatic effects on neurite outgrowth in appropriate circumstances. Several of these factors have been shown to exist in appropriate positions to promote neurite growth in vivo as well as in vitro. The response of neurons to such factors depends on-Cheir growth state-.- This presentation will focus on characterization of these neurite outgrowth promoting factors and our efforts to determine their roles in directing neuronal development. The role of ECM compo- nents in directing axon growth and guidance in vivo is poorly understood . The Study of soluble factors, which conta1.n ECM components and act when bound to a substratum, may offer insights into that role. Supported by gi:-;rnts from the Niil, NSF, March of Dimes, and MDA.

Neurons require appropriate substrata on which to extend neurites and the composition of the substrata encountered in vivo is believed to regulate both the extent and direction of axon growth as well as the position at which synaptic specializations appear.
In particular, three constituents of extracellular matrix--fibronectin, laminin, and factors associated with heparan sulfate proteoglycans--have dramatic effects on neurite outgrowth in appropriate circumstances. Several of these factors have been shown to exist in appropriate positions to promote neurite growth in vivo as well as in vitro.
The response of neurons to such factors depends on their growth state. This presentation will focus on characterization of these neurite outgrowth promoting factors and our efforts to determine their roles in directing neuronal development.
The role of ECM components in directing axon growth and guidance in vivo is poorly understood.
The study of soluble factors, which contain ECM components and act when bound to a substratum, may offer insights into that role.
Supported by grants from the NIH, NSF, March of Dimes, and MDA.

Functional and structural characterization of cell surface antige~ L1
Schachner, M., Faissner, A., Kruse, J., Lindner, ,]. and Rathjen, ~ . Dept. of Neurobiol., Univ. Heidelberg, Heidelberg, W. Germany Migration of granule cell neurons in the developing mouse cerebellar cortex and a Ca ++ independent adhesion mechanism between cerebellar and C1300 neuroblastoma cells are inhibited by Fab fragments of antibodies to cel] surface antigen I]. Both, polyand monoclonal antibodies to LI antigen react predominantly with postmitotic neurons in the central nervous system.
In the peripheral nervous system the antigen is detectable on Schwann cells in addition to neurons.
The antigen consists of two bands in SDS polyacrylamide gels with apparent molecular weights of ]40 and 200 kilodaltons at all ages studied.
Chemical deglycosylation leads to a single band of 70 kilodaltons.
In visual cortex of albinorats weakly GAD positive cells appear in a characteristic spatio-temporal sequence: in lamina I about embryonic day 18 (E18); in subplate between E20 and postnatal day 4 (P4) with a gradient from periphery to center of the visual region; in cortical plate P2 to P5.
Laminas IIl+ IV are further delayed until about P8 to PIO.
The number of CAD positive cells reaches adult density during the 2nd p.n. week.
Pericarya and stem dendrites become GAD reactive 2 to 7 days before GAD positive axon terminals appear.
Adult terminal density is attained 3 to 4 weeks p.n.
In neurons GAD increases during 2 weeks after birth, but GAD density varies greatly even in adult GABA-ergic neurons.
CAD reactivity was always restricted to nonpyram~dal neurons.