Migrating and myelinating potential of neural precursors engineered to overexpress PSA-NCAM.
Polysialic acid (PSA) on NCAM is an important modulator of cell-cell interactions during development and regeneration. Here we investigated whether PSA overexpression influences neural cell migration and myelination. We stably expressed a GFP-tagged polysialytransferase, PSTGFP, in mouse neurospheres and induced prolonged PSA synthesis. Using a chick xenograft assay for migration, we show that PSA can instruct precursor migration along the ventral pathway. PSA persistence did not change neural precursor multipotentiality in vitro but induced a delay in oligodendrocyte differentiation. PSTGFP+ precursors showed widespread engraftment in shiverer brain, closely similar to that observed with control precursors expressing a fluorescent protein. Initially, myelination by oligodendrocytes was delayed but, eventually, down-regulation of PSTGFP occurred, allowing myelination to proceed. Thus down-regulation of polysialyltransferases takes place even in cells where its RNA is under the control of a heterologous promoter and engineering PSA overexpression in neural precursors does not cause irreversible unphysiological effects.
Unité de Neurovirologie et Régénération du Système Nerveux, Institut Pasteur, 75724 Paris cedex 15, France.
Isabelle
I
Franceschini
Sandrine
S
Vitry
Françoise
F
Padilla
Philippe
P
Casanova
To Nam
TN
Tham
Minoru
M
Fukuda
Geneviève
G
Rougon
Pascale
P
Durbec
Monique
M
Dubois-Dalcq
D016475:3T3 Cells; D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009413:Nerve Fibers, Myelinated / Q000378:metabolism* / Q000637:transplantation; D039842:Neural Cell Adhesion Molecule L1 / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000378:metabolism* / Q000637:transplantation; D015202:Protein Engineering / Q000379:methods; D012794:Sialic Acids / Q000096:biosynthesis* / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism*
D039842:Neural Cell Adhesion Molecule L1; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule