of LN are mediated by integrin ol^/^^ heterodimers. 
Preliminary evidence indicates that integrin ct^^/Pj 
heterodimers may also be able to bind to the El-4 
fragment. To summarize these results, there now 
appear to be at least three integrin a/p^ hetero- 
dimers capable of binding to LN. 
Individual integrin a/p^ heterodimers have been 
' identified as receptors for LN, FN, and the colla- 
gens. There is also evidence that heterodimers in 
the Pj family recognize additional ligands, such as 
tenascin and vitronectin, for which heterodimeric 
receptors have not been identified. Dr. Blaise Bossy 
and Karla Neugebauer have tried to identify these 
additional receptors. They have shown that the 
integrin a-subunit, (x^, previously shown to as- 
sociate with Pj and P^, can also associate with Pj. 
The ligand-binding properties of the (x^/p^ are 
being investigated. Dr. Bossy has also sequenced 
cDNAs encoding a novel integrin a-subunit. Using 
antibodies prepared to peptides in the sequence of 
this novel integrin, he has shown that it is an a-sub- 
unit of M 150,000 that associates with the 6 -sub- 
unit. The novel heterodimer has now been puri- 
fied. Its ligand-binding properties are being 
examined. 
In earlier work, the functions of several integrin 
Pj-receptors were shown to be regulated during de- 
velopment of embryonic chick retinal neurons and 
ciliary neurons. In particular, target contact appears 
to downregulate LN-binding integrins. In the past 
year. Dr. Ivan de Curtis and Dr. Hall have shown 
that these changes correlate with the loss of indi- 
vidual integrin a-subunits. 
III. Neuronal Adhesion and Process Extension on 
Cellular Substrates. 
In earlier work. Dr. Reichardt and his colleagues 
showed that both ECM glycoproteins and cell adhe- 
sion molecules can function as promoters of axon 
extension. The relative importance of individual 
molecules depends on both the type and age of the 
neurons and the particular cellular substrate. On 
most cells, multiple independent interactions ap- 
pear to function to promote neurite outgrowth. On 
PUBLICATIONS 
Schwann cells, for example, ciliary neurons were 
shown to extend neurites by using integrin Pj 
heterodimers to interact with the ECM proteins as- 
sembled on the Schwann cell surface. The most im- 
portant of these was shown to be an isoform of LN. 
The same neurons also use N-cadherin on the 
growth cone to interact with N-cadherin expressed 
on the surface of the Schwann cells and Ll/Ng-CAM 
on the growth cone to interact with Ll/Ng-CAM on 
the Schwann cell surface. Dr. Frances Lefcort has 
been examining regulation of these integrins and 
cell adhesion molecules in developing and dener- 
vated peripheral nerve. She has evidence that all of 
these glycoproteins are regulated by denervation. 
Most are induced, but N-cadherin is actually 
downregulated by denervation. Mechanisms of reg- 
ulation are being explored. 
In previous work studying neuronal interactions 
with astroglia. Dr. Reichardt and his colleagues 
demonstrated roles for both p^ and p^ integrins and 
several cell adhesion molecules. Results also indi- 
cated that additional adhesive interactions were im- 
portant but were mediated by uncharacterized re- 
ceptors and ligands. Motivated by these 
observations. Dr. Gene Napolitano and Kristine 
Venstrom have begun an effort to identify novel cell 
adhesion molecules. As the first step in this project, 
they prepared antibodies to peptides correspond- 
ing to sequences found in all characterized 
cadherins (N, P, and E). In collaboration with Dr. 
Jack Lilien (University of Wisconsin), these antibod- 
ies were shown to recognize each of the character- 
ized cadherins and several additional glycoproteins 
in the neuroretina with properties consistent with 
the possibility that they represent novel cadherins. 
Pursuing this possibility. Dr. Napolitano isolated 
cDNAs encoding proteins recognized by the 
cadherin-specific antibodies, one of which has now 
been shown to encode a novel cadherin. Studies to 
demonstrate its function and distribution are being 
pursued. 
Dr. Reichardt is also Professor of Physiology and 
of Biochemistry and Biophysics at the University of 
California at San Francisco. 
Books and Chapters of Books 
Clegg, D.O., Large, T.L., Bodary S C., Shelton, D.L., and Reichardt, L.F. 1989. Quantitative measurement of 
nerve growth factor mRNA. In Neuronal Growth Factors (Rush, R.A., Ed.). New York: Wiley, pp 255-275. 
(IBRO Handbook Series.) 
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