The developmental origin of oligodendrocyte progenitors (OLPs) in the forebrain has been controversial. We now show, by Cre-lox fate mapping in transgenic mice, that the first OLPs originate in the medial ganglionic eminence (MGE) and anterior entopeduncular area (AEP) in the ventral forebrain. From there, they populate the entire embryonic telencephalon including the cerebral cortex before being joined by a second wave of OLPs from the lateral and/or caudal ganglionic eminences (LGE and CGE). Finally, a third wave arises within the postnatal cortex. When any one population is destroyed at source by the targeted expression of diphtheria toxin, the remaining cells take over and the mice survive and behave normally, with a normal complement of oligodendrocytes and myelin. Thus, functionally redundant populations of OLPs compete for space in the developing brain. Notably, the embryonic MGE- and AEP-derived population is eliminated during postnatal life, raising questions about the nature and purpose of the competition.

Cortical pyramidal cells are generated from pallial neuroepithelial precursors, whereas GABAergic interneurons originate in subpallial germinal zones and migrate tangentially to reach the cortex. Using Cre-lox technology in transgenic mice and a series of molecular markers that subdivide the subpallial neuroepithelium into small domains, we fate-map precursor pools and identify interneurons generated from each domain. Cortical interneurons expressing calbindin, parvalbumin, and somatostatin are generated exclusively from Lhx6 (Lim homeobox 6)-expressing precursors in the medial ganglionic eminence (MGE). Martinotti cells that coexpress calretinin and somatostatin are generated from the dorsal region of the MGE neuroepithelium that expresses Nkx6.2 (NK2 transcription factor-related 6.2). Most neuropeptide Y-expressing cells and all bipolar calretinin-expressing interneurons are generated outside the MGE, from the germinal zones of the lateral/caudal ganglionic eminences that express Gsh2 (genomic screened homeobox 2). Our data demonstrate that subpallial neuroepithelial domains defined by expression of genetic determinants generate distinct interneuron subtypes, thereby contributing to the generation of cortical interneuron heterogeneity observed in the adult cortex.

SummaryNew myelin-forming oligodendrocytes (OLs) are generated in the mouse central nervous system during adulthood. These adult-born OLs might augment the existing population, contributing to neural plasticity, or else replace OLs that die in use (turnover). To distinguish between these alternatives, we induced genetic labeling of mature myelinating OLs in young adult mice and tracked their subsequent survival. OL survival rates were region dependent, being higher in corpus callosum (∼90% survival over 20 months) and motor cortex (∼70% survival) than in corticospinal tract or optic nerve (50%–60% survival). Survival rates over the first 8 months were 90%–100% in all regions except the optic nerve. In the corpus callosum, new OLs accumulate during young adulthood and are therefore likely to participate in adaptive myelination. We also found that the number of myelin internodes maintained by individual cortical OLs is stable for at least 8 months but declines ∼12% in the following year.

The lack of markers for astrocytes, particularly gray matter astrocytes, significantly hinders research into their development and physiological properties. We previously reported that fibroblast growth factor receptor 3 (Fgfr3) is expressed by radial precursors in the ventricular zone of the embryonic neural tube and subsequently by differentiated astrocytes in gray and white matter. Here, we describe an Fgfr3-iCreER(T2) phage artificial chromosome transgenic mouse line that allows efficient tamoxifen-induced Cre recombination in Fgfr3-expressing cells, including radial glial cells in the embryonic neural tube and both fibrous and protoplasmic astrocytes in the mature central nervous system. This mouse strain will therefore be useful for studies of normal astrocyte biology and their responses to CNS injury or disease. In addition, Fgfr3-iCreER(T2) drives Cre recombination in all neurosphere-forming stem cells in the adult spinal cord and at least 90% of those in the adult forebrain subventricular zone. We made use of this to show that there is continuous accumulation of all major interneuron subtypes in the olfactory bulb (OB) from postnatal day 50 (P50) until at least P230 ( approximately 8 months of age). It therefore seems likely that adult-born interneurons integrate into existing circuitry and perform long-term functions in the adult OB.

Remyelination is the regenerative response to demyelination. Although the oligodendrocyte progenitor is established as the major source of remyelinating cells, there is no conclusive evidence on whether mature, differentiated oligodendrocytes can also contribute to remyelination. Using two different inducible myelin-CreER mouse strains in which mature oligodendrocytes were prelabeled by the expression of membrane-bound Green fluorescent protein, we found that after focal spinal cord demyelination, the surrounding surviving labeled oligodendrocytes did not proliferate but remained at a consistent density. Furthermore, existing (prelabeled) oligodendrocytes showed no evidence of incorporation or migration into the lesioned area, or of process extension from the peripheral margins into the lesion. Thus, mature oligodendrocytes do not normally contribute to remyelination and are therefore not a promising target for regenerative therapy.

Motor skill learning stimulates and requires generation of myelinating oligodendrocytes (OLs) from their precursors. We asked whether OL production is also required for non- motor learning and cognition, using T-maze and radial arm maze tasks that tax spatial working memory. Maze training stimulated OL production in the medial prefrontal cortex, anterior corpus callosum (genu), hippocampus and fimbria; myelin sheath formation was also stimulated in the genu. Genetic blockade of OL differentiation and neo-myelination in Myrf conditional knockout mice strongly impaired training-induced improvements in maze performance. Remarkably, working memory performance of individual mice correlated closely with the scale of OL precursor proliferation and OL generation in their genu and anterior cingulate cortex during training, indicating a key role for adaptive OL genesis and myelination in cognitive processing.

Co-ordinate measuring systems based on theodolites are increasingly being found in industrial environments. The paper explains the principles on which the technique is based, the system components and the factors which affect the accuracy that can be achieved. Finally some application areas are listed and a particular example from the aircraft industry is highlighted.Process Photogrammetry Theodolite system Positioning of units J J Photography J Orientation measurement J J Adjustment (bundle) J J Measurement J J Analysis J J \ / Automation Y Common solution? 72 1

The article discusses a general classification system applicable to digital ground models (D.G.M.) as used in highway design. Examples of the various categories are given, together with details of some advantages and disadvantages. The place of the D.G.M. in the highway design system is described in conjunction with traditional methods. The relationship between accuracy, density and economy of D.G.M. systems is examined. Finally an experiment is described which investigates the accuracy of various D.G.M. systems; it is being conducted by the Transport and Road ResearchLaboratory.