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PMID:17760872

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Citation

Ries, A, Goldberg, JL and Grimpe, B (2007) A novel biological function for CD44 in axon growth of retinal ganglion cells identified by a bioinformatics approach. J. Neurochem. 103:1491-505

Abstract

The failure of CNS regeneration and subsequent motor and sensory loss remain major unsolved questions despite massive accumulation of experimental observations and results. The sheer volume of data and the variety of resources from which these data are generated make it difficult to integrate prior work to build new hypotheses. To address these challenges we developed a prototypic suite of computer programs to extract protein names from relevant publications and databases and associated each of them with several general categories of biological functions in nerve regeneration. To illustrate the usefulness of our data mining approach, we utilized the program output to generate a hypothesis for a biological function of CD44 interaction with osteopontin (OPN) and laminin in axon outgrowth of CNS neurons. We identified CD44 expression in retinal ganglion cells and when these neurons were plated on poly-l-lysine 3% of them initiated axon growth, on OPN 15%, on laminin-111 (1x) 41%, on laminin-111 (0.5x) 56%, and on a mixture of OPN and laminin (1x) 67% of neurons generated axon growth. With the aid of a deoxyribozyme (DNA enzyme) to CD44 that digests the target mRNA, we demonstrated that a reduction of CD44 expression led to reduced axon initiation of retinal ganglion cells on all substrates. We suggest that such an integrative, applied systems biology approach to CNS trauma will be critical to understand and ultimately overcome the failure of CNS regeneration.

Links

PubMed PMC2901540 Online version:10.1111/j.1471-4159.2007.04858.x

Keywords

Animals; Antigens, CD44/physiology; Axons/physiology; Cell Differentiation/physiology; Cell Proliferation; Cells, Cultured; Computational Biology/methods; Computational Biology/trends; Rats; Rats, Sprague-Dawley; Retinal Ganglion Cells/cytology; Retinal Ganglion Cells/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:CD44

involved_in

GO:0031175: neuron projection development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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