A focused and efficient genetic screening strategy in the mouse: identification of mutations that disrupt cortical development.
Although the mechanisms that regulate development of the cerebral cortex have begun to emerge, in large part through the analysis of mutant mice (Boncinelli et al. 2000; Molnar and Hannan 2000; Walsh and Goffinet 2000), many questions remain unanswered. To provide resources for further dissecting cortical development, we have carried out a focused screen for recessive mutations that disrupt cortical development. One aim of the screen was to identify mutants that disrupt the tangential migration of interneurons into the cortex. At the same time, we also screened for mutations that altered the growth or morphology of the cerebral cortex. We report here the identification of thirteen mutants with defects in aspects of cortical development ranging from the establishment of epithelial polarity to the invasion of thalamocortical axons. Among the collection are three novel alleles of genes for which mutant alleles had already been used to explore forebrain development, and four mutants with defects in interneuron migration. The mutants that we describe here will aid in deciphering the molecules and mechanisms that regulate cortical development. Our results also highlight the utility of focused screens in the mouse, in addition to the large-scale and broadly targeted screens that are being carried out at mutagenesis centers.
Department of Neurology and the Ernest Gallo Clinic and Research Center, University of California at San Francisco, Emeryville, USA.
Konstantinos
K
Zarbalis
Scott R
SR
May
Yiguo
Y
Shen
Marc
M
Ekker
John L R
JL
Rubenstein
Andrew S
AS
Peterson
D000483:Alleles; D000818:Animals; D001369:Axons; D002465:Cell Movement; D002540:Cerebral Cortex / Q000473:pathology*; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000235:genetics; D004330:Drosophila; D005038:Ethylnitrosourea / Q000494:pharmacology; D005121:Extremities / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D007395:Interneurons / Q000166:cytology; D007763:Lac Operon; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000235:genetics / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D000071701:Regulatory Factor X Transcription Factors; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics; D019076:Transgenes; D025521:Tumor Suppressor Proteins / Q000502:physiology
D004268:DNA-Binding Proteins; D026561:Low Density Lipoprotein Receptor-Related Protein-2; C055127:Lrp2 protein, mouse; D008565:Membrane Proteins; D000071701:Regulatory Factor X Transcription Factors; C479564:Rfx4 protein, mouse; C480591:SCRIB protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D049452:Green Fluorescent Proteins; D005038:Ethylnitrosourea