Abstract
The multilayeredmammalianneocortex develops by the coordinated immigration and differentiation of cells that are produced at distant sites. Correct layering requires an extracellular protein, Reelin (Reln), an intracellular signaling molecule, Disabled-1 (Dab1), and an E3 ubiquitin ligase, Cullin-5 (Cul5). Reln activates Dab1, which is then degraded by Cul5. Herewetest whether Cul5 regulates neuron layering by affecting Dab1 stability or other mechanisms. We find that a stabilized mutant Dab1, which resists Cul5-dependent degradation, causes a similar phenotype to Cul5 deficiency. Moreover, Cul5 has no effect when Dab1 is absent. The effects of Cul5 and Dab1 are cell autonomous, and Cul5 regulates movement of early as well as late cortical neurons. Removing Cul5 increases the speed at which neurons migrate through the cortical plate by reducing the time spent stationary and increasing the speed of individual steps. These results show that Cul5 regulates neuron layering by stimulating Dab1 degradation and that Cul5 controls migration speed and stopping point, and they demonstrate the importance of negative feedback in signaling during cortical development. Copyright
| Original language | English (US) |
|---|---|
| Pages (from-to) | 5668-5676 |
| Number of pages | 9 |
| Journal | Journal of Neuroscience |
| Volume | 30 |
| Issue number | 16 |
| DOIs | |
| State | Published - Apr 21 2010 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Neuroscience(all)
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Cullin 5 regulates cortical layering by modulating the speed and duration of Dab1-dependent neuronal migration. / Simo Olivar, Sergi; Jossin, Yves; Cooper, Jonathan A.
In: Journal of Neuroscience, Vol. 30, No. 16, 21.04.2010, p. 5668-5676.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cullin 5 regulates cortical layering by modulating the speed and duration of Dab1-dependent neuronal migration
AU - Simo Olivar, Sergi
AU - Jossin, Yves
AU - Cooper, Jonathan A.
PY - 2010/4/21
Y1 - 2010/4/21
N2 - The multilayeredmammalianneocortex develops by the coordinated immigration and differentiation of cells that are produced at distant sites. Correct layering requires an extracellular protein, Reelin (Reln), an intracellular signaling molecule, Disabled-1 (Dab1), and an E3 ubiquitin ligase, Cullin-5 (Cul5). Reln activates Dab1, which is then degraded by Cul5. Herewetest whether Cul5 regulates neuron layering by affecting Dab1 stability or other mechanisms. We find that a stabilized mutant Dab1, which resists Cul5-dependent degradation, causes a similar phenotype to Cul5 deficiency. Moreover, Cul5 has no effect when Dab1 is absent. The effects of Cul5 and Dab1 are cell autonomous, and Cul5 regulates movement of early as well as late cortical neurons. Removing Cul5 increases the speed at which neurons migrate through the cortical plate by reducing the time spent stationary and increasing the speed of individual steps. These results show that Cul5 regulates neuron layering by stimulating Dab1 degradation and that Cul5 controls migration speed and stopping point, and they demonstrate the importance of negative feedback in signaling during cortical development. Copyright
AB - The multilayeredmammalianneocortex develops by the coordinated immigration and differentiation of cells that are produced at distant sites. Correct layering requires an extracellular protein, Reelin (Reln), an intracellular signaling molecule, Disabled-1 (Dab1), and an E3 ubiquitin ligase, Cullin-5 (Cul5). Reln activates Dab1, which is then degraded by Cul5. Herewetest whether Cul5 regulates neuron layering by affecting Dab1 stability or other mechanisms. We find that a stabilized mutant Dab1, which resists Cul5-dependent degradation, causes a similar phenotype to Cul5 deficiency. Moreover, Cul5 has no effect when Dab1 is absent. The effects of Cul5 and Dab1 are cell autonomous, and Cul5 regulates movement of early as well as late cortical neurons. Removing Cul5 increases the speed at which neurons migrate through the cortical plate by reducing the time spent stationary and increasing the speed of individual steps. These results show that Cul5 regulates neuron layering by stimulating Dab1 degradation and that Cul5 controls migration speed and stopping point, and they demonstrate the importance of negative feedback in signaling during cortical development. Copyright
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UR - http://www.scopus.com/inward/citedby.url?scp=77951559070&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.0035-10.2010
DO - 10.1523/JNEUROSCI.0035-10.2010
M3 - Article
C2 - 20410119
AN - SCOPUS:77951559070
VL - 30
SP - 5668
EP - 5676
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 16
ER -