EXPRESSION OF HB-GAM (HEPARIN-BINDING GROWTH-ASSOCIATED MOLECULES) INTHE PATHWAYS OF DEVELOPING AXONAL PROCESSES IN-VIVO AND NEURITE OUTGROWTH IN-VITRO INDUCED BY HB-GAM

Citation
H. Rauvala et al., EXPRESSION OF HB-GAM (HEPARIN-BINDING GROWTH-ASSOCIATED MOLECULES) INTHE PATHWAYS OF DEVELOPING AXONAL PROCESSES IN-VIVO AND NEURITE OUTGROWTH IN-VITRO INDUCED BY HB-GAM, Developmental brain research, 79(2), 1994, pp. 157-176
Citations number
73
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences
ISSN journal
0165-3806
Volume
79
Issue
2
Year of publication
1994
Pages
157 - 176
Database
ISI
SICI code
0165-3806(1994)79:2<157:EOH(GM>2.0.ZU;2-S
Abstract
HB-GAM (heparin-binding growth-associated molecule; p18) was previousl y isolated as a neurite outgrowth-promoting protein that is expressed at high levels in perinatal rat brain. cDNA cloning and expression rev ealed that HB-GAM is a novel secretory protein that is homologous with the retinoic acid-inducible MK protein. In the present paper we have used affinity-purified anti-peptide and anti-protein antibodies to stu dy the expression of HB-GAM in the developing nervous system of the ra t. In general, HB-GAM accumulates to extracellular structures that lin e growing axonal processes but is absent or only occurs at low levels in the axonal pathways after neurite extension has essentially ceased. During early stages of the nervous system development, HB-GAM is stro ngly expressed in the developing fiber tracts of the peripheral nervou s system on embryonic days 12-14 (E12-E14). In the early central nervo us system, HB-GAM is first expressed in a radial pattern along the neu roepithelial cells on E11-E12 and in early ascending neuron fibers in superficial layers of the brain vesicles on E12-E14. On E16-E18, HB-GA M is strongly expressed in the subplate and the marginal zone of the p rimordial neocortex. After this local expression in the primordial bra in, HB-GAM is more widely expressed in the pathways of the developing axons during the late embryonic and early postnatal period. We have al so extended in vitro studies on the interactions of HB-GAM with perina tal rat brain neurons by creating patterned substrates of HB-GAM upon culture wells and upon mixtures of extracellular matrix structures. Th ese studies confirm the neurite-promoting effect of HB-GAM and suggest , together with the patterns of tissue localization, that HB-GAM may a lso guide axonal processes of brain neurons. The interactions of HB-GA M with brain neurons are specifically inhibited by heparin and its fra gments and by incubation of the neurons with heparitinase. We suggest that in developing nervous tissues HB-GAM is deposited to an extracell ular location in developing axon pathways and it interacts with hepari n-like molecules of the neuron surface to promote formation of neural connections.