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.

CEITEC Central European Institute of Technology Brno University of Technology Brno Czechia

Center for Brain Research Medical University Vienna Vienna Austria

Department of Basic Science Faculty of Medicine University of Crete Heraklion Greece

Department of Biology Massachusetts Institute of Technology Cambridge MA United States

Department of Molecular Medicine Max Planck Institute of Biochemistry Martinsried Germany

Department of Physiology and Pharmacology Karolinska Institutet Stockholm Sweden

Foundation for Research and Technology Institute of Molecular Biology and Biotechnology Heraklion Greece

Laboratory of Neurophysiology Université Libre de Bruxelles UNI Brussels Belgium

The Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology Cambridge MA United States

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Contrast enhanced X-ray computed tomography imaging of amyloid plaques in Alzheimer disease rat model on lab based micro CT system