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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Cell. Neurosci. | doi: 10.3389/fncel.2019.00454

Ablation of CNTN2+ pyramidal neurons during development results in defects in neocortical size and axonal tract formation

 Maria E. Kastriti1, 2, 3, 4, Aikaterini Stratigi1, 2, 5,  Marina Theodosiou1, 2, 6, Maria Savvaki1, 2,  Dimitris Mariatos1, 2,  Michaela Kavkova7,  Kostas Theodorakis1, 2, Marina Vidaki1, 2, 8, 9,  Tomas Zikmund7,  Jozef Kaiser7,  Igor Adameyko3, 4 and  Domna Karagogeos1, 2*
  • 1Division of Basic Sciences, School of Medicine, University of Crete, Greece
  • 2Institute of Molecular Biology and Biotechnology (IMBB), Foundation of Research and Technology (FORTH), Greece
  • 3Department of Physiology and Pharmacology, Karolinska Institutet, Sweden
  • 4Center for Brain Research, Medical University of Vienna, Austria
  • 5Laboratory of Neurophysiology and Movement Biomechanics (LNMB), Free University of Brussels, Belgium
  • 6Department of Molecular Medicine, Max Planck Institute of Biochemistry, Germany
  • 7Central European Institute of Technology, Brno University of Technology, Czechia
  • 8Koch Institute for Integrative Cancer Research at MIT, United States
  • 9Department of Biology, School of Science, Massachusetts Institute of Technology, United States

Corticothalamic axons express Contactin-2 (CNTN2/TAG-1), a neuronal recognition molecule of the immunoglobulin superfamily involved in neurogenesis, neurite outgrowth and fasciculation. TAG-1, which is expressed transiently by cortical pyramidal neurons during embryonic development, has been shown to be fundamental for axonal recognition, cellular migration and neuronal proliferation in the developing cortex. Although Tag-1-/- mice do not exhibit any obvious defects in the corticofugal system, the role of TAG-1+ neurons during the development of the cortex remains elusive. We have generated a mouse model expressing EGFP under the Tag-1 promoter and encompassing the coding sequence of Diptheria Toxin subunit A (DTA) under quiescence with no effect on the expression of endogenous Tag-1. We show that while the line recapitulates the expression pattern of the molecule, it highlights an extended expression in the forebrain, including multiple axonal tracts and neuronal populations, both spatially and temporally. Crossing these mice to the Emx1-Cre strain, we ablated the vast majority of TAG-1+ cortical neurons. Among the observed defects were a significantly smaller cortex, a reduction of corticothalamic axons as well as callosal and commissural defects. Such defects are common in neurodevelopmental disorders, thus this mouse could serve as a useful model to study physiological and pathophysiological cortical development.

Keywords: CNTN2/TAG-1, Corticofugal system, Corticothalamic axons, anterior commissure, Corpus Callosum, Central Nervous System

Received: 22 May 2019; Accepted: 23 Sep 2019.

Copyright: © 2019 Kastriti, Stratigi, Theodosiou, Savvaki, Mariatos, Kavkova, Theodorakis, Vidaki, Zikmund, Kaiser, Adameyko and Karagogeos. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Domna Karagogeos, Division of Basic Sciences, School of Medicine, University of Crete, Heraklion, Greece, karagoge@imbb.forth.gr