Robo1 regulates the development of major axon tracts and interneuron migration in the forebrain

Andrews, W., Liapi, A., Plachez, C., Camurri, L., Zhang, J. Y., Mori, S., Murakami, F., Parnavelas, J. G., Sundaresan, V. and Richards, L. J. (2006) Robo1 regulates the development of major axon tracts and interneuron migration in the forebrain. Development, 133 11: 2243-2252. doi:10.1242/dev.02379

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Author Andrews, W.
Liapi, A.
Plachez, C.
Camurri, L.
Zhang, J. Y.
Mori, S.
Murakami, F.
Parnavelas, J. G.
Sundaresan, V.
Richards, L. J.
Title Robo1 regulates the development of major axon tracts and interneuron migration in the forebrain
Journal name Development   Check publisher's open access policy
ISSN 0950-1991
Publication date 2006-06-01
Year available 2006
Sub-type Article (original research)
DOI 10.1242/dev.02379
Open Access Status File (Publisher version)
Volume 133
Issue 11
Start page 2243
End page 2252
Total pages 10
Editor Jim Smith
Place of publication Cambridge
Publisher Company Of Biologists Ltd
Language eng
Subject C1
270210 Neurogenetics
270106 Cell Development (incl. Cell Division and Apoptosis)
730104 Nervous system and disorders
Abstract The Slit genes encode secreted ligands that regulate axon branching, commissural axon pathfinding and neuronal migration. The principal identified receptor for Slit is Robo ( Roundabout in Drosophila). To investigate Slit signalling in forebrain development, we generated Robo1 knockout mice by targeted deletion of exon 5 of the Robo1 gene. Homozygote knockout mice died at birth, but prenatally displayed major defects in axon pathfinding and cortical interneuron migration. Axon pathfinding defects included dysgenesis of the corpus callosum and hippocampal commissure, and abnormalities in corticothalamic and thalamocortical targeting. Slit2 and Slit1/2 double mutants display malformations in callosal development, and in corticothalamic and thalamocortical targeting, as well as optic tract defects. In these animals, corticothalamic axons form large fasciculated bundles that aberrantly cross the midline at the level of the hippocampal and anterior commissures, and more caudally at the medial preoptic area. Such phenotypes of corticothalamic targeting were not observed in Robo1 knockout mice but, instead, both corticothalamic and thalamocortical axons aberrantly arrived at their respective targets at least 1 day earlier than controls. By contrast, in Slit mutants, fewer thalamic axons actually arrive in the cortex during development. Finally, significantly more interneurons ( up to twice as many at E12.5 and E15.5) migrated into the cortex of Robo1 knockout mice, particularly in both rostral and parietal regions, but not caudal cortex. These results indicate that Robo1 mutants have distinct phenotypes, some of which are different from those described in Slit mutants, suggesting that additional ligands, receptors or receptor partners are likely to be involved in Slit/Robo signalling.
Keyword Thalamocortical Axons
Corpus Callosum
Hippocampal Commissure
Axon Guidance
Cell Migration
Developmental Biology
Cortical Interneurons
Ganglionic Eminence
Neuronal Migration
Directional Guidance
Expression Patterns
Mammalian Forebrain
Cns Midline
Dlx Genes
Q-Index Code C1
Grant ID EB003543-01A
Institutional Status UQ

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Created: Wed, 15 Aug 2007, 19:11:56 EST