Gene profiling and bioinformatic analysis of Schwann cell embryonic development and myelination.
To elucidate the molecular mechanisms involved in Schwann cell development, we profiled gene expression in the developing and injured rat sciatic nerve. The genes that showed significant changes in expression in developing and dedifferentiated nerve were validated with RT-PCR, in situ hybridisation, Western blot and immunofluorescence. A comprehensive approach to annotating micro-array probes and their associated transcripts was performed using Biopendium, a database of sequence and structural annotation. This approach significantly increased the number of genes for which a functional insight could be found. The analysis implicates agrin and two members of the collapsin response-mediated protein (CRMP) family in the switch from precursors to Schwann cells, and synuclein-1 and alphaB-crystallin in peripheral nerve myelination. We also identified a group of genes typically related to chondrogenesis and cartilage/bone development, including type II collagen, that were expressed in a manner similar to that of myelin-associated genes. The comprehensive function annotation also identified, among the genes regulated during nerve development or after nerve injury, proteins belonging to high-interest families, such as cytokines and kinases, and should therefore provide a uniquely valuable resource for future research.
D'Antonio
Maurizio
M
Department of Anatomy and Developmental Biology, University College London, London, United Kingdom.
Michalovich
David
D
Paterson
Morris
M
Droggiti
Anna
A
Woodhoo
Ashwin
A
Mirsky
Rhona
R
Jessen
Kristjan R
KR
D018171:Agrin / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D019295:Computational Biology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D047108:Embryonic Development / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D017403:In Situ Hybridization; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D009186:Myelin Sheath / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D009432:Neural Crest / Q000166:cytology / Q000196:embryology; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012583:Schwann Cells / Q000502:physiology*; D020426:Sciatic Neuropathy / Q000473:pathology; D038203:alpha-Crystallin B Chain / Q000096:biosynthesis / Q000235:genetics; D051844:alpha-Synuclein / Q000096:biosynthesis / Q000235:genetics; D000098855:Collapsin Response Mediator Protein 1
D018171:Agrin; D016207:Cytokines; C485779:Dpysl4 protein, rat; D016209:Interleukin-8; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; C497606:Snca protein, rat; D038203:alpha-Crystallin B Chain; D051844:alpha-Synuclein; D000098855:Collapsin Response Mediator Protein 1; D003994:Bucladesine