Dopamine receptor activation modulates GABA neuron migration from the basal forebrain to the cerebral cortex

GABA neurons of the cerebral cortex and other telencephalic structures are produced in the basal forebrain and migrate to their final destinations during the embryonic period. The embryonic basal forebrain is enriched in dopamine and its receptors, creating a favorable environment for dopamine to influence GABA neuron migration. However, whether dopamine receptor activation can influence GABA neuron migration is not known. We show that dopamine D1 receptor activation promotes and D2 receptor activation decreases GABA neuron migration from the medial and caudal ganglionic eminences to the cerebral cortex in slice preparations of embryonic mouse forebrain. Slice preparations from D1 or D2 receptor knock-out mouse embryos confirm the findings. In addition, D1 receptor electroporation into cells of the basal forebrain and pharmacological activation of the receptor promote migration of the electroporated cells to the cerebral cortex. Analysis of GABA neuron numbers in the cerebral wall of the dopamine receptor knock-out mouse embryos further confirmed the effects of dopamine receptor activation on GABA neuron migration. Finally, dopamine receptor activation mobilizes striatal neuronal cytoskeleton in a manner consistent with the effects on neuronal migration. These data show that impairing the physiological balance between D1 and D2 receptors can alter GABA neuron migration from the basal forebrain to the cerebral cortex. The intimate relationship between dopamine and GABA neuron development revealed here may offer novel insights into developmental disorders such as schizophrenia, attention deficit or autism, and fetal cocaine exposure, all of which are associated with dopamine and GABA imbalance

Increased frequency of homologous recombination and T-DNA integration in Arabidopsis CAF-1 mutants

Chromatin assembly factor 1 (CAF-1) is involved in nucleo some assembly following DNA replication and nucleotide excision repair. In Arabidopsis thaliana, the three CAF-1 subunits are encoded by FAS1, FAS2 and, most likely, MSI1, respectively. In this study, we asked whether genomic stability is altered in fas1 and fas2 mutants that are lacking CAF-1 activity. Depletion of either subunit increased the frequency of somatic homologous recombination (HR) in planta ∼40-fold. The frequency of transferred DNA (T-DNA) integration was also elevated. A delay in loading histones onto newly replicated or repaired DNA might make these DNA stretches more accessible, both to repair enzymes and to foreign DNA. Furthermore, fas mutants exhibited increased levels of DNA double-strand breaks, a G2-phase retardation that accelerates endoreduplication, and elevated levels of mRNAs coding for proteins involved in HR—all factors that could also contribute to upregulation of HR frequency in fas mutants