Directional guidance of interneuron migration to the cerebral cortex relies on subcortical Slit1/2-independent repulsion and cortical attraction.
Tangential migration from the basal telencephalon to the cortex is a highly directional process, yet the mechanisms involved are poorly understood. Here we show that the basal telencephalon contains a repulsive activity for tangentially migrating cells, whereas the cerebral cortex contains an attractive activity. In vitro experiments demonstrate that the repulsive activity found in the basal telencephalon is maintained in mice deficient in both Slit1 and Slit2, suggesting that factors other than these are responsible for this activity. Correspondingly, in vivo analysis demonstrates that interneurons migrate to the cortex in the absence of Slit1 and Slit2, or even in mice simultaneously lacking Slit1, Slit2 and netrin 1. Nevertheless, loss of Slit2 and, even more so, Slit1 and Slit2 results in defects in the position of other specific neuronal populations within the basal telencephalon, such as the cholinergic neurons of the basal magnocellular complex. These results demonstrate that whereas Slit1 and Slit2 are not necessary for tangential migration of interneurons to the cortex, these proteins regulate neuronal migration within the basal telencephalon by controlling cell positioning close to the midline.
Marín
Oscar
O
Department of Psychiatry, Nina Ireland Laboratory of Developmental Neurobiology, Langley Porter Psychiatric Institute, 401 Parnassus Avenue, University of California-San Francisco, CA 94143, USA.
Plump
Andrew S
AS
Flames
Nuria
N
Sánchez-Camacho
Cristina
C
Tessier-Lavigne
Marc
M
Rubenstein
John L R
JL
D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002540:Cerebral Cortex / Q000196:embryology* / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D007395:Interneurons / Q000502:physiology*; D051379:Mice; D009414:Nerve Growth Factors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D000075388:Netrin-1; D025521:Tumor Suppressor Proteins; D000098552:Slit Homolog 2 Protein
D036341:Intercellular Signaling Peptides and Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C000617353:Ntn1 protein, mouse; C120010:Slit1 protein, mouse; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1; D000098552:Slit Homolog 2 Protein