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.
Franceschini
Isabelle
I
Unité de Neurovirologie et Régénération du Système Nerveux, Institut Pasteur, 75724 Paris cedex 15, France.
Vitry
Sandrine
S
Padilla
Françoise
F
Casanova
Philippe
P
Tham
To Nam
TN
Fukuda
Minoru
M
Rougon
Geneviève
G
Durbec
Pascale
P
Dubois-Dalcq
Monique
M
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