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NATURE REVIEWS | NEUROSCIENCE VOLUME 5 | OCTOBER 2004 | 741

In the developing spinal cord, oligo-dendrocyte production is restricted toa narrow ventral domain by theopposing actions of an inductive,ventrally-derived sonic hedgehog signal and an inhibitory, dorsally-derived bone morphogenetic protein(BMP) signal. In a recent paper inDevelopment, Samanta and Kesslerpresent new evidence that the inhib-itory effects of BMP4 on oligoden-drogenesis are mediated by membersof the inhibitor of differentiation(ID) protein family.

The authors cultured mouseneural progenitor cells under condi-tions that normally promote the speci-fication of the oligodendrocyte lineage. BMP4 caused a reduction inoligodendrocyte differentiation and acorresponding increase in astrocyteproduction in these cultures. BMP4also induced the expression of all four ID family members (ID1–4).Overexpression of Id2 and Id4, but notId1 or Id3, mimicked the inhibitoryeffects of BMP4 on oligodendrogene-sis. Id4 was the more potent inhibitor,and the combined overexpression ofId2 and Id4 had a similar effect to Id4alone. Moreover, the authors foundthat they could block the inhibitoryeffects of BMP4 by using RNA inter-ference to inhibit Id4 expression.

The ID proteins have a helix–loop–helix domain, which enablesthem to dimerize with basic helix–loop–helix (bHLH) proteins, butthey lack a DNA-binding domain.

The ID proteins seem to inhibit oligo-dendrogenesis by interacting withbHLH transcription factors. In theoligodendrocyte lineage, the class BbHLH factors OLIG1 and OLIG2,which are required for oligodendroge-nesis, dimerize with class A bHLH fac-tors, including the E2A proteins E12and E47. These heterodimers translo-cate to the nucleus, where they activatethe genetic pathways that induceoligodendrocyte differentiation. Usinga co-immunoprecipitation assay,Samanta and Kessler showed that bothID4 and ID2 could bind to the OLIGproteins, and that all four ID proteinscould bind to the E2A proteins.Whenneural precursor cells were treatedwith BMP4, the intracellular localiza-tion of the OLIG proteins changedfrom predominantly nuclear to pre-dominantly cytoplasmic.

Taken together, these findingspoint to a mechanism in which IDproteins function in a dominant-nega-tive manner to sequester the OLIGproteins — and perhaps also the E2Aproteins — in the cytoplasm, therebypreventing them from entering thenucleus and activating their targetgenes.

Heather Wood

References and linksORIGINAL RESEARCH PAPER Samanta, J. &Kessler, J. A. Interactions between ID and OLIGproteins mediate the inhibitory effects of BMP4 onoligodendroglial differentiation. Development 131,4131–4142 (2004)FURTHER READING Rowitch, D. H. Glialspecification in the vertebrate neural tube. NatureRev. Neurosci. 5, 409–419 (2004)

Shh

BMP

E12.5 E14.5 E18.5

Pre-migratory phase Migratory phase

VZ

Oligodendrocytes don’t need ID

G L I O G E N E S I S IN BRIEF

Forgetting, reminding and remembering: the retrieval oflost spatial memory.de Hoz, L. et al. PLoS Biol. 2, 1233–1242 (2004)

An important question in the study of memory is whetherretrograde amnesia represents a deficit in memory storage orretrieval. Rats with a partial lesion of the hippocampus, whichprevented them from remembering the location of the platform ina water maze task, could be ‘reminded’ of the original location ofthe platform by an escape platform in another location. Bydistinguishing reminding from new place learning, this study showsthat a disruption in retrieval can contribute to retrograde amnesia.

Preclinical vCJD after blood transfusion in a PRNPcodon 129 heterozygous patient.Peden, A. H. et al. Lancet 364, 527–529 (2004)

The authors describe a patient who was found, at post-mortem, tohave preclinical signs of vCJD (variant Creutzfeld–Jakob disease).The patient had received a blood transfusion 5 years previouslyfrom a donor who went on to develop vCJD. Althoughheterozygosity at codon 129 of the prion protein gene PRNP hasbeen thought to protect against vCJD, this patient washeterozygous at codon 129. It might be that heterozygotes are notprotected, but have a longer incubation period; alternatively, theymight be vulnerable to infection but not to the disease.

Visual pattern recognition in Drosophila is invariant forretinal position.Tang, S. et al. Science 305, 1020–1022 (2004)

Translation invariance is the ability to recognize visual patternsindependent of their retinal location. In previous studies,Drosophila melanogaster were unable to recognize patterns thatwere presented in a new region of the visual field. However, thestimulus features that were manipulated might have beenoccluded by vertical displacements of the stimuli. In this study,which used stimuli that varied in size and colour, flies showedpattern recognition independent of retinal position.

The contribution of spike threshold to the dichotomy ofcortical simple and complex cells.Prieb, N. J. et al. Nature Neurosci. 29 August 2004 (10.1038/nn1310)

Simple and complex cells in the cat primary visual cortex areoften distinguished by the ratio between modulated andunmodulated components of spike responses to drifting gratings.If the modulation ratio is taken from the subthreshold membranepotential instead of the spike rate, it is unimodally distributed.However, the nonlinear properties of the spike threshold, whenapplied to this distribution, define the two classes of neuron.

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Schematic diagram showing oligodendrocyte-specific marker expression (blue) between embryonic day (E)12.5 and E18.5 in the mouse spinal cord. Oligodendrocytes are generated in a restricted domain in theventral half of the neural tube, and they are dispersed throughout the spinal cord during the migratory phase.