The neuroanatomy of Eml1 knockout mice, a model of subcortical heterotopia

J Anat. 2019 Sep;235(3):637-650. doi: 10.1111/joa.13013. Epub 2019 Jun 7.


The cerebral cortex is a highly organized structure responsible for advanced cognitive functions. Its development relies on a series of steps including neural progenitor cell proliferation, neuronal migration, axonal outgrowth and brain wiring. Disruption of these steps leads to cortical malformations, often associated with intellectual disability and epilepsy. We have generated a new resource to shed further light on subcortical heterotopia, a malformation characterized by abnormal neuronal position. We describe here the generation and characterization of a knockout (KO) mouse model for Eml1, a microtubule-associated protein showing mutations in human ribbon-like subcortical heterotopia. As previously reported for a spontaneous mouse mutant showing a mutation in Eml1, we observe severe cortical heterotopia in the KO. We also observe abnormal progenitor cells in early corticogenesis, likely to be the origin of the defects. EML1 KO mice on the C57BL/6N genetic background also appear to present a wider phenotype than the original mouse mutant, showing additional brain anomalies, such as corpus callosum abnormalities. We compare the anatomy of male and female mice and also study heterozygote animals. This new resource will help unravel roles for Eml1 in brain development and tissue architecture, as well as the mechanisms leading to severe subcortical heterotopia.

Keywords: cortical malformations; heterotopia; mouse model of developmental disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / pathology*
  • Classical Lissencephalies and Subcortical Band Heterotopias / embryology
  • Classical Lissencephalies and Subcortical Band Heterotopias / genetics
  • Classical Lissencephalies and Subcortical Band Heterotopias / pathology*
  • Disease Models, Animal
  • Female
  • Male
  • Mice, Knockout
  • Microtubule-Associated Proteins / physiology*


  • Eml1 protein, mouse
  • Microtubule-Associated Proteins