Genomic imprinting and the maternal brain.
Those parts of the genome that contain imprinted genes are relatively small (between 100 and 150 genes predicted) but their impact on mammalian development and evolution is substantial. Most of the imprinted genes that have been studied are regulatory: transcription factors, alternative splicers, oncogenes, tumor suppressors, growth factors, or are involved in complex signalling pathways such as the tumor necrosis factor (TNF) and ubiquitin pathways. This review considers the effects of imprinted genes on brain development by examining the distribution of androgenetic and parthenogenetic cells in the brains of chimeric mice using in situ markers. At birth, cells that are disomic for the paternal genome (androgenetic) contribute substantially to the hypothalamus, septum, preoptic area and bed nuclei of the stria terminalis and fail to survive in the developing neocortex and striatum. In contrast, cells that are disomic for the maternal genome (parthenogenetic) proliferate in the cortex and striatum but are excluded from the diencephalic structures. Growth of the brain is enhanced by the presence of parthenogenetic cells and hence increased maternal gene dosage, whereas the brains of androgenetic chimeras are smaller. Mest and Peg3, two imprinted genes that are paternally expressed, have been disrupted by gene targeting and show high levels of expression in regions where androgenetic cells accumulated, namely the hypothalamus, preoptic area and septum. Although of different structural classes and located on different chromosomes, both of these paternally expressed genes influence placental growth and maternal behavior. The implications of these findings for brain evolution and maternal behavior are discussed.
Keverne
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EB
Sub-Department of Animal Behaviour, University of Cambridge, High Street, Madingley, Cambridge CB3 8AA, UK. ebk10@cus.cam.ac.uk
D000818:Animals; D005075:Biological Evolution; D001921:Brain / Q000254:growth & development / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D008322:Mammals; D008425:Maternal Behavior / Q000502:physiology*