Molecular genetic approaches to understanding brain development and behaviour

An understanding of brain development and brain function at the level of the genome is developing rapidly, because of the availability of new technologies in molecular and cellular biology. This understanding can be further enhanced by an interactive exchange between the disciplines of behavioural neuroscience and molecular genetics. New genes are being cloned almost daily, but their function remains an enigma. The purpose of this review is to illustrate how reporter genes can be used to map the brain's genetic activity in developmental time and anatomical space. The production of mutants in the homozygous condition may further lead to a morphological or behavioural phenotype. A knowledge of behavioural neuroscience can provide a prescreen of the reporter distribution and thereby make predictions concerning the type of behavioural analysis required. This approach allows selective cloning and sequencing of those genes which have either a morphological or behavioural phenotype but are transcribed at low levels. It is known that genomic imprinting influences brain development, and also that human genetic mutations and deletions influence imprinting in mental retardation as well as certain behavioural disorders. Precisely how such imprinted genes influence brain development and behaviour is being pursued by the use of chimeras. The distribution of maternal or paternal disomy cells in the brain and the way they influence behaviour may reveal the phenotype and how this is brought about.

[1]  J. Hall,et al.  How imprinting is relevant to human disease. , 1990, Development.

[2]  W. Reik Genomic imprinting and genetic disorders in man. , 1989, Trends in genetics : TIG.

[3]  B. Cattanach,et al.  Autosomal and X-chromosome imprinting. , 1990, Development (Cambridge, England). Supplement.

[4]  R. Lerner,et al.  Identifier sequences are transcribed specifically in brain , 1984, Nature.

[5]  M. McInnis,et al.  Genes with triplet repeats: candidate mediators of neuropsychiatric disorders , 1993, Trends in Neurosciences.

[6]  M. Wigler,et al.  Cloning the differences between two complex genomes , 1993, Science.

[7]  Allan Bradley,et al.  Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice , 1991, Cell.

[8]  C. Sapienza,et al.  Parental imprinting of genes. , 1990, Scientific American.

[9]  M. Capecchi,et al.  Altering the genome by homologous recombination. , 1989, Science.

[10]  J. Horgan,et al.  Bufo abuse. A toxic toad gets licked, boiled, teed up and tanned. , 1990, Scientific American.

[11]  Chris Graham,et al.  Genomic imprinting and the strange case of the insulin-like growth factor II receptor , 1991, Cell.

[12]  R. Nicoll,et al.  An essential role for postsynaptic calmodulin and protein kinase activity in long-term potentiation , 1989, Nature.

[13]  W. Hahn,et al.  Genetic expression in the developing brain. , 1983, Science.

[14]  A. Pardee,et al.  Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction. , 1992, Science.

[15]  T. Moore,et al.  Genomic imprinting in mammalian development: a parental tug-of-war. , 1991, Trends in genetics : TIG.

[16]  The Production of Transgenic Mice , 1993 .

[17]  M. Surani,et al.  Temporal and spatial selection against parthenogenetic cells during development of fetal chimeras. , 1990, Development.

[18]  E. Keverne,et al.  A position-dependent transgene reveals patterns of gene expression in the developing brain. , 1990, Brain research. Developmental brain research.

[19]  A. Ghysen,et al.  Neural enhancer-like elements as specific cell markers in Drosophila. , 1989, Development.

[20]  R. Tsien,et al.  Inhibition of postsynaptic PKC or CaMKII blocks induction but not expression of LTP. , 1989, Science.

[21]  D. Solter Differential imprinting and expression of maternal and paternal genomes. , 1988, Annual review of genetics.

[22]  Philippe Soriano,et al.  Promoter traps in embryonic stem cells: a genetic screen to identify and mutate developmental genes in mice. , 1991, Genes & development.

[23]  M. Surani,et al.  Genomic imprinting: developmental significance and molecular mechanism. , 1991, Current opinion in genetics & development.

[24]  Alcino J. Silva,et al.  Impaired spatial learning in alpha-calcium-calmodulin kinase II mutant mice. , 1992, Science.

[25]  M. Surani,et al.  Influence of paternally imprinted genes on development. , 1991, Development.

[26]  M. Surani,et al.  Developmental consequences of imprinting of parental chromosomes by DNA methylation. , 1990, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[27]  Elly Nedivi,et al.  Numerous candidate plasticity-related genes revealed by differential cDNA cloning , 1993, Nature.

[28]  A. Joyner,et al.  Mouse embryonic stem cells and reporter constructs to detect developmentally regulated genes. , 1989, Science.

[29]  D. G. Cran,et al.  Transgenes as probes for active chromosomal domains in mouse development , 1988, Nature.

[30]  J. Rossant,et al.  Of fin and fur: mutational analysis of vertebrate embryonic development. , 1992, Genes & development.

[31]  W. Gehring,et al.  Detection in situ of genomic regulatory elements in Drosophila. , 1987, Proceedings of the National Academy of Sciences of the United States of America.