Perissinotto, Daniela and Iacopetti, Paola and Bellina, Isabella and Doliana, Roberto and Colombatti, Alfonso and Pettway, Zoé and Shinomura, Tamayuki and Kimata, Koji and Mörgelin, Matthias and Löfberg, Jan and Perris, Roberto and Bronner, Marianne E. (2000) Avian neural crest cell migration is diversely regulated by the two major hyaluronan-binding proteoglycans PG-M/versican and aggrecan. Development, 127 (13). pp. 2823-2842. ISSN 0950-1991 http://resolver.caltech.edu/CaltechAUTHORS:20111209-073948808
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It has been proposed that hyaluronan-binding proteoglycans play an important role as guiding cues during neural crest (NC) cell migration, but their precise function has not been elucidated. In this study, we examine the distribution, structure and putative role of the two major hyaluronan-binding proteoglycans, PG-M/versicans and aggrecan, during the course of avian NC development. PG-M/versicans V0 and V1 are shown to be the prevalent isoforms at initial and advanced phases of NC cell movement, whereas the V2 and V3 transcripts are first detected following gangliogenesis. During NC cell dispersion, mRNAs for PG-M/versicans V0/V1 are transcribed by tissues lining the NC migratory pathways, as well as by tissues delimiting nonpermissive areas. Immunohistochemistry confirm the deposition of the macromolecules in these regions and highlight regional differences in the density of these proteoglycans. PG-M/versicans assembled within the sclerotome rearrange from an initially uniform distribution to a preferentially caudal localization, both at the mRNA and protein level. This reorganization is a direct consequence of the metameric NC cell migration through the rostral portion of the somites. As suggested by previous in situ hybridizations, aggrecan shows a virtually opposite distribution to PG-M/versicans being confined to the perinotochordal ECM and extending dorsolaterally in a segmentally organized manner eventually to the entire spinal cord at axial levels interspacing the ganglia. PG-M/versicans purified from the NC migratory routes are highly polydispersed, have an apparent M(r) of 1,200-2,000 kDa, are primarily substituted with chondroitin-6-sulfates and, upon chondroitinase ABC digestion, are found to be composed of core proteins with apparent M(r)of 360–530, 000. TEM/rotary shadowing analysis of the isolated PG-M/versicans confirmed that they exhibit the characteristic bi-globular shape, have core proteins with sizes predicted for the V0/V1 isoforms and carry relatively few extended glycosaminoglycan chains. Orthotopical implantation of PG-M/versicans immobilized onto transplantable micromembranes tend to ‘attract’ moving cells toward them, whereas similar implantations of a notochordal type-aggrecan retain both single and cohorts of moving NC cells in close proximity of the implant and thereby perturb their spatiotemporal migratory pattern. NC cells fail to migrate through three-dimensional collagen type I-aggrecan substrata in vitro, but locomote in a haptotactic manner through collagen type I-PG-M/versican V0 substrata via engagement of HNK-1 antigen-bearing cell surface components. The present data suggest that PG-M/versicans and notochordal aggrecan exert divergent guiding functions during NC cell dispersion, which are mediated by both their core proteins and glycosaminoglycan side chains and may involve ‘haptotactic-like’ motility phenomena. Whereas aggrecan defines strictly impenetrable embryonic areas, PG-M/versicans are central components of the NC migratory pathways favoring the directed movement of the cells.
|Additional Information:||© 2000 The Company of Biologists. Accepted 11 April; published on WWW 13 June 2000. We thank Elena Gabriele, Michela Zanbon and Maria Teresa Mucignat for their technical assistance, Paola Spessotto for her assistance with the confocal laser microscopy, Gianluca Tell for performing HPLC chromatographies, and Guido David, Dick Heinegård, Firoz Rahemtulla and Michael Sorrell for their proteoglycan and antibody contribution. The work was supported by grants from Associazione Italiana della Ricerca sul Cancro (AIRC) and Fondo Sanitario Nazionale (FSN, RF-95 and RF-96).|
|Subject Keywords:||PG-M/versican, Neural crest, Cell migration, Aggrecan, Proteoglycan, Chick|
|Official Citation:||D. Perissinotto, P. Iacopetti, I. Bellina, R. Doliana, A. Colombatti, Z. Pettway, M. Bronner-Fraser, T. Shinomura, K. Kimata, M. Morgelin, J. Lofberg, and R. Perris Avian neural crest cell migration is diversely regulated by the two major hyaluronan-binding proteoglycans PG-M/versican and aggrecan Development 2000 127:2823-2842|
|Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Ruth Sustaita|
|Deposited On:||09 Dec 2011 16:48|
|Last Modified:||26 Dec 2012 14:35|
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