Cullin 5 regulates cortical layering by modulating the speed and duration of Dab1-dependent neuronal migration

Sergi Simo Olivar, Yves Jossin, Jonathan A. Cooper

Research output: Contribution to journalArticle

41 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)5668-5676
Number of pages9
JournalJournal of Neuroscience
Volume30
Issue number16
DOIs
StatePublished - Apr 21 2010
Externally publishedYes

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Cullin Proteins
Neurons
Intracellular Signaling Peptides and Proteins
Ubiquitin-Protein Ligases
Emigration and Immigration
Cerebral Cortex
Cell Differentiation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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 journalArticle

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