Lis1 Is Necessary for Normal Non-Radial Migration of Inhibitory Interneurons

McManus, Matthew F.; Nasrallah, Ilya M.; Pancoast, Maclean M.; Wynshaw‐Boris, Anthony; Golden, Jeffrey A.

doi:10.1016/s0002-9440(10)63340-8

Cited by 93 publications

(84 citation statements)

References 45 publications

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“…The distinction between radial and tangential migration may be blurred somewhat in the RMS, as neurons undergo chain migration but through a substrate of glial guidance. A similar requirement for LIS1 and components of the reelin pathway in both radial and tangential migration have reported 18,[60][61][62] .…”

Section: As a Regulator Of Radial And Tangential Migrationsupporting

confidence: 66%

Doublecortin maintains bipolar shape and nuclear translocation during migration in the adult forebrain

et al. 2006

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The ability of the mature mammalian nervous system to continually produce neuronal precursors is of considerable importance, as manipulation of this process might one day permit the replacement of cells lost as a result of injury or disease. In mammals, the anterior subventricular zone (SVZa) region is one of the primary sites of adult neurogenesis. Here we show that Doublecortin (DCX), a widely used marker for newly generated neurons, when deleted in mouse results in a severe morphological defect in the rostral migratory stream and delayed neuronal migration that is independent of direction or responsiveness to Slit chemorepulsion. DCX is required for nuclear translocation and maintenance of bipolar morphology during migration of these cells. Our data identifies a critical function for DCX in the movement of newly generated neurons in the adult brain.In the rodent and primate brain, the anterior region of the lateral ventricle and the hippocampus are the primary sites of adult neurogenesis [1][2][3][4][5][6][7] . These neuroblasts, upon completing migration, are capable of maturing into fully differentiated neurons, integrating into local synaptic circuits and may be important in adult cognitive processing [8][9][10][11] .The mechanisms controlling the targeted translocation of large numbers of cells to the olfactory bulb (OB) over a considerable distance (>5 mm in the adult mouse) are an issue of intense investigation. These neurons translocate using a process known as chain migration, whereby the cells use each other as the migratory substrate 12 . These newly generated neurons are derived from SVZa glial fibrillary acidic protein (GFAP)-positive astrocytes 13,14 , which also ensheath them as they move through extensive interconnected networks along the lining of the lateral ventricle in the rostral forebrain and the rostral migratory stream (RMS) 15 . There, they are under the control of extracellular migration guidance cues, including the secreted ligands Slit and Reelin [16][17][18][19] , the receptors ErbB4 and Deleted in Colorectal Carcinoma (DCC) 20,21 , as well as integrins and neural cell adhesion molecule [21][22][23] . Upon reaching the bulb, the neurons turn and migrate in a radial direction 24 , integrating into either the granule cell layer or the periglomerular network 25 . 3The X-linked gene doublecortin (DCX) is mutated in some patients with the severe neuronal migration defect called classical lissencephaly or double cortex syndrome 26,27 . This migration defect is likely to be cell autonomous, because in females with a heterozygous mutation, approximately half of the neurons are misplaced within the cerebral cortex as would be expected from random X-chromosome inactivation. As a result, males display a four-layered agyric cortex and females display a subcortical band of heterotopic neurons. It was surprising, therefore, that the Dcx knockout mice displayed no appreciable defect in cortical neuronal lamination or positioning 28 . One possible explanation for these species differences ...

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Section: As a Regulator Of Radial And Tangential Migrationsupporting

confidence: 66%

Doublecortin maintains bipolar shape and nuclear translocation during migration in the adult forebrain

et al. 2006

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“…However, current evidence suggests that many of these mutants display defects in both modes of migration (McManus et al, 2004;Kappeler et al, 2006;this study). Impairment in the migration, disposition, and proper integration of interneurons in the cortical circuitry may explain, at least in part, the epilepsy and mental retardation observed in lissencephaly.…”

Section: Cortical Interneurons In Dclk and DCX Mutant Micementioning

confidence: 84%

“…Specifically, McManus et al (2004) have reported that LIS1-deficient interneurons migrate more slowly than wildtype cells in brain slices prepared from E14.5 Lis1 knock-out mice. The defects in cortical interneuron migration that result from inactivation of DCX or LIS1 resemble the reported impairment in radial migration of pyramidal neurons after DCX RNAi in combination with in utero electroporation in rat embryonic brain (Bai et al, 2003).…”

Section: Interneuron Migration Is Delayed After DCX Rnaimentioning

confidence: 99%

Both Doublecortin and Doublecortin-Like Kinase Play a Role in Cortical Interneuron Migration

Friocourt¹,

Liu²,

Antypa³

et al. 2007

J. Neurosci.

137

119

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Type I lissencephaly, a genetic disease characterized by disorganized cortical layers and gyral abnormalities, is associated with severe cognitive impairment and epilepsy. Two genes, LIS1 and doublecortin (DCX), have been shown to be responsible for a large proportion of cases of type I lissencephaly. Both genes encode microtubule-associated proteins that have been shown to be important for radial migration of cortical pyramidal neurons. To investigate whether DCX also plays a role in cortical interneuron migration, we inactivated DCX in the ganglionic eminence of rat embryonic day 17 brain slices using short hairpin RNA. We found that, when DCX expression was blocked, the migration of interneurons from the ganglionic eminence to the cerebral cortex was slowed but not absent, similar to what had previously been reported for radial neuronal migration. In addition, the processes of DCX-deficient migrating interneurons were more branched than their counterparts in control experiments. These effects were rescued by DCX overexpression, confirming the specificity to DCX inactivation. A similar delay in interneuron migration was observed when Doublecortin-like kinase (DCLK), a microtubuleassociated protein related to DCX, was inactivated, although the morphology of the cells was not affected. The importance of these genes in interneuron migration was confirmed by our finding that the cortices of Dcx, Dclk, and Dcx/Dclk mutant mice contained a reduced number of such cells in the cortex and their distribution was different compared with wild-type controls. However, the defect was different for each group of mutant animals, suggesting that DCX and DCLK have distinct roles in cortical interneuron migration.

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“…Mice heterozygous for a Lis1 null allele display only mild defects in neuronal migration, but further reduction of Lis1 levels by combining a null allele with a hypomorphic Lis1 allele profoundly disrupts cortical lamination (Gambello et al 2003;Hirotsune et al 1998). In many Lis1-deficient neurons, the extension of the leading process is unaffected (but see McManus et al 2004), suggesting that the perturbed neuronal migration most likely results from defects in nucleokinesis (Shu et al 2004;Tanaka et al 2004;Tsai and Gleeson 2005). Lis1 associates with microtubules and a subpopulation of Lis1 localizes to the centrosome.…”

Section: Nucleokinesismentioning

confidence: 99%

“…Although the function of Lis1, DCX, DCLK, and CDK5 in nucleokinesis has been primarily studied in radially migrating cells, analysis of other neuronal populations suggests that they play a universal role in this process (Friocourt et al 2007;Kappeler et al 2006;McManus et al 2004;Nasrallah et al 2006;Rakić et al 2009). …”

Section: Nucleokinesismentioning

confidence: 99%

Guiding Neuronal Cell Migrations

Marı́n¹,

Valiente²,

Ge³

et al. 2010

Cold Spring Harbor Perspectives in Biology

366

351

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Neuronal migration is, along with axon guidance, one of the fundamental mechanisms underlying the wiring of the brain. As other organs, the nervous system has acquired the ability to grow both in size and complexity by using migration as a strategy to position cell types from different origins into specific coordinates, allowing for the generation of brain circuitries. Guidance of migrating neurons shares many features with axon guidance, from the use of substrates to the specific cues regulating chemotaxis. There are, however, important differences in the cell biology of these two processes. The most evident case is nucleokinesis, which is an essential component of migration that needs to be integrated within the guidance of the cell. Perhaps more surprisingly, the cellular mechanisms underlying the response of the leading process of migrating cells to guidance cues might be different to those involved in growth cone steering, at least for some neuronal populations.

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Lis1 Is Necessary for Normal Non-Radial Migration of Inhibitory Interneurons

Cited by 93 publications

References 45 publications

Doublecortin maintains bipolar shape and nuclear translocation during migration in the adult forebrain

Doublecortin maintains bipolar shape and nuclear translocation during migration in the adult forebrain

Both Doublecortin and Doublecortin-Like Kinase Play a Role in Cortical Interneuron Migration

Guiding Neuronal Cell Migrations

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