Deleted in colorectal carcinoma and differentially expressed integrins mediate the directional migration of neural precursors in the rostral migratory stream.
Precursors of the olfactory interneurons migrate from the subventricular zone via the rostral migratory stream (RMS). To investigate the molecular mechanisms by which RMS cells migrate, we used a slice preparation, which allows the migrating cells to be imaged at very high temporal and spatial resolution in the presence of added inhibitors. Using immunohistochemistry, we first determined that the alpha1-, beta8-, and beta1-integrin subunits and the alpha5- and gamma1-laminin subunits are expressed during embryonic day 16 to the early postnatal stage. During early postnatal days, alpha(v)- and beta6-integrins appeared, and their expression persisted throughout adulthood. The migrating cells also expressed the netrin receptors neogenin and Deleted in Colorectal Carcinoma (DCC). Netrin-1 is expressed in olfactory mitral cells. Anti-integrin antibodies inhibited the production of protrusions as well as cellular translocation. In contrast, anti-DCC antibodies primarily altered the direction of the protrusions; consequently, the migration was no longer unidirectional, and the speed was reduced. Thus, the interaction of DCC, possibly through an interaction with netrin-1, contributes to the direction of migration by regulating the formation of directed protrusions. In contrast, the integrins function in production of protrusions and cellular translocation, with different integrins participating at different developmental stages.
Murase
Shin-ichi
S
Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA. sm4fh@virginia.edu
Horwitz
Alan F
AF
D000375:Aging / Q000378:metabolism; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D000075389:DCC Receptor; D005456:Fluorescent Dyes; D066298:In Vitro Techniques; D016023:Integrins / Q000096:biosynthesis* / Q000502:physiology; D007797:Laminin / Q000096:biosynthesis; D020547:Lateral Ventricles / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018715:Microscopy, Video; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules / Q000096:biosynthesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology / Q000378:metabolism; D011956:Receptors, Cell Surface; D012794:Sialic Acids / Q000096:biosynthesis; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D014741:Video Recording
D015815:Cell Adhesion Molecules; D000075389:DCC Receptor; C501910:Dcc protein, mouse; D005456:Fluorescent Dyes; D016023:Integrins; D007797:Laminin; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules; D011956:Receptors, Cell Surface; D012794:Sialic Acids; D025521:Tumor Suppressor Proteins; C103469:polysialyl neural cell adhesion molecule