Mitotic spindle regulation by Nde1 controls cerebral cortical size

Yuanyi Feng, Christopher A. Walsh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

298 Scopus citations


Ablation of the LIS1-interacting protein Nde1 (formerly mNudE) in mouse produces a small brain (microcephaly), with the most dramatic reduction affecting the cerebral cortex. While cortical lamination is mostly preserved, the mutant cortex has fewer neurons and very thin superficial cortical layers (II to IV). BrdU birthdating revealed retarded and modestly disorganized neuronal migration; however, more dramatic defects on mitotic progression, mitotic orientation, and mitotic chromosome localization in cortical progenitors were observed in Nde1 mutant embryos. The small cerebral cortex seems to reflect both reduced progenitor cell division and altered neuronal cell fates. In vitro analysis demonstrated that Nde1 is essential for centrosome duplication and mitotic spindle assembly. Our data show that mitotic spindle function and orientation are essential for normal development of mammalian cerebral cortex.

Original languageEnglish (US)
Pages (from-to)279-293
Number of pages15
Issue number2
StatePublished - Oct 14 2004

ASJC Scopus subject areas

  • Neuroscience(all)


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