Defining brain wiring patterns and mechanisms through gene trapping in mice

P A Leighton; K J Mitchell; L V Goodrich; X Lu; K Pinson; P Scherz; W C Skarnes; M Tessier-Lavigne

doi:10.1038/35065539

Defining brain wiring patterns and mechanisms through gene trapping in mice

Nature. 2001 Mar 8;410(6825):174-9. doi: 10.1038/35065539.

Authors

P A Leighton¹, K J Mitchell, L V Goodrich, X Lu, K Pinson, P Scherz, W C Skarnes, M Tessier-Lavigne

Affiliation

¹ Howard Hughes Medical Institute and Department of Anatomy, University of California, San Francisco, California 94143-0452, USA.

PMID: 11242070
DOI: 10.1038/35065539

Abstract

The search to understand the mechanisms regulating brain wiring has relied on biochemical purification approaches in vertebrates and genetic approaches in invertebrates to identify molecular cues and receptors for axon guidance. Here we describe a phenotype-based gene-trap screen in mice designed for the large-scale identification of genes controlling the formation of the trillions of connections in the mammalian brain. The method incorporates an axonal marker, which helps to identify cell-autonomous mechanisms in axon guidance, and has generated a resource of mouse lines with striking patterns of axonal labelling, which facilitates analysis of the normal wiring diagram of the brain. Studies of two of these mouse lines have identified an in vivo guidance function for a vertebrate transmembrane semaphorin, Sema6A, and have helped re-evaluate that of the Eph receptor EphA4.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkaline Phosphatase / genetics
Animals
Axons / physiology*
Brain / anatomy & histology
Brain / embryology
Brain / enzymology
Brain / physiology*
Cell Adhesion Molecules, Neuronal / genetics
Cell Adhesion Molecules, Neuronal / physiology
Cell Movement
Cells, Cultured
Female
Fetal Proteins / genetics
Fetal Proteins / physiology
GPI-Linked Proteins
Genetic Techniques*
Genetic Vectors
Humans
Isoenzymes / genetics
Male
Mice
Mice, Inbred C57BL
Mutation
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / physiology*
Neural Pathways
Neurons / physiology
Phenotype
Receptor Protein-Tyrosine Kinases / genetics
Receptor Protein-Tyrosine Kinases / physiology
Receptor, EphA4
Ribosomes / genetics
Semaphorins
Sensory Receptor Cells / physiology*
Thalamus / abnormalities
Thalamus / metabolism

Substances

Cell Adhesion Molecules, Neuronal
Fetal Proteins
GPI-Linked Proteins
Isoenzymes
Nerve Tissue Proteins
SEMA6A protein, human
Sema6a protein, mouse
Semaphorins
Receptor Protein-Tyrosine Kinases
Receptor, EphA4
Alkaline Phosphatase
alkaline phosphatase, placental