Το γονίδιο Cux2 στην ανάπτυξη των ενδιάμεσων νευρώνων του φλοιού
The Cux2 gene encodes a homeodomain transcription factor which is strongly expressed in the
vertebrate nervous system during development. It is one of the two orthologue genes of the
Drosophila cut gene which patterns a specific sensory organ in the peripheral nervous system and has
been implicated in the regulation of dendritic branching in the central nervous system. During mouse
development Cux2 is expressed in a group of progenitors in the subventricular zone (SVZ) of the
dorsal telencephalon and in interneurons migrating from the ganglionic eminences into the pallium.
In postnatal and adult animals CUX2 is localized mainly in the upper layers and sparsely in the lower
layers of the cortex. Previous studies have shown that CUX2, together with CUX1 regulate the
dendritic branching, spine development and synaptic formation in layers II-III of the cortex. Also,
CUX2 regulates the proliferation rates in the cortical SVZ and the numbers of neurons in the upper
layers of the cortex. Until now, the contribution of CUX2 in the formation of different GABAergic
interneuron populations in the cortex has been poorly assessed.
In this project we investigated the possible roles of CUX2 in the development of cortical
interneurons. We used a conditional knock-out mouse model (Nkx2.1-Cre; Cux2 fl/Δ) in which CUX2
was deleted in interneurons derived from the medial ganglionic eminence (MGE), one of the two
major sources of interneurons for the cortex. Our results, deriving from immunohistochemistry and
in situ hybridization analysis, suggest 1) an increase in PV-expressing interneuron numbers and 2) an
increase in soma- and axon initial segment-targeting inhibitory synapses in the cortex. These results
are supported by electrophysiological data showing raised inhibition, as a functional consequence of
CUX2 deletion in cortical circuits. Finally, behavioural assessment revealed defects in sociability.