Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic expansion of glia and cell autonomous responses to Egfr dosage

Development of the nervous system undergoes important transitions, including one from neurogenesis to gliogenesis which occurs late during embryonic gestation. Here we report on clonal analysis of gliogenesis in mice using Mosaic Analysis with Double Markers (MADM) with quantitative and computational methods. Results reveal that developmental gliogenesis in the cerebral cortex occurs in a fraction of earlier neurogenic clones, accelerating around E16.5, and giving rise to both astrocytes and oligodendrocytes. Moreover, MADM-based genetic deletion of the epidermal growth factor receptor (Egfr) in gliogenic clones revealed that Egfr is cell autonomously required for gliogenesis in the mouse dorsolateral cortices. A broad range in the proliferation capacity, symmetry of clones, and competitive advantage of MADM cells was evident in clones that contained one cellular lineage with double dosage of Egfr relative to their environment, while their sibling Egfr-null cells failed to generate glia. Remarkably, the total numbers of glia in MADM clones balance out regardless of significant alterations in clonal symmetries. The variability in glial clones shows stochastic patterns that we define mathematically, which are different from the deterministic patterns in neuronal clones. This study sets a foundation for studying the biological significance of stochastic and deterministic clonal principles underlying tissue development, and identifying mechanisms that differentiate between neurogenesis and gliogenesis.</jats:p

Direct n.c.a. radioiodination of weakly activated arenes using metal salts

The direct electrophilic no-carrier-added (n.c.a.) aromatic radioiodination was examined using various metal salts in trifluoroacetic acid (TFA) as in situ oxidation agents. Two different types of metal salts were used comprising TFA-soluble (Pb(CH3CO2)(4), Mn(CH3CO2)(3), KMnO4, Tl(CF3CO2)(3), AgCF3SO3) and TFA-insoluble (Ce(CF3SO3)(4), RuCl3, FeBr3, K2Cr2O7) salts. Optimization of both labelling systems has been performed using Pb(CH3CO2)(4), Ce(CF3SO3)(4) and benzene as a model substrate. At room temperature, the one-pot synthesis was completed within 15 min, resulting in a radiochemical yield of 82% and 64% using Pb(CH3CO2)(4) and Ce(CF3SO3)(4), respectively. Radioiodination of weakly activated monosubstituted benzene derivatives led to high radiochemical yields of about 80% and 60% of the corresponding ortho- and para-radioiodo-isomers using both salts. Weakly deactivated chlorobenzene could only be radioiodinated with Ce(CF3SO3)(4) as oxidant, forming exclusively the para-product with a radiochemical yield of about 35 %. Using the optimized reaction parameters for the other TFA-soluble and -insoluble metal salts with benzene and toluene good radiochemical yields were obtained in all cases except for the manganese and silver salts. Apparently their oxidation power was not strong enough for the radioiodination of the non-activated benzenes. In situ formed trifluoroacetyl [I-131]hypoiodite is discussed with regard to the reaction mechanism

Beiträge zum Verhalten der Petroleumabfallschwefelsäure und ihre Verwendung in der Superphosphatfabrikation

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