The nuclear orphan receptor COUP-TFI is required for differentiation of subplate neurons and guidance of thalamocortical axons

Chicken ovalbumin upstream promotor-transcription factor I (COUP-TFI), an o rphan member of the nuclear receptor superfamily, is highly expressed in th e developing nervous systems. In the cerebral cortex of Coup-tfl mutants, c ortical layer IV was absent due to excessive cell death, a consequence of t he failure of thalamocortical projections. Moreover, subplate neurons under went improper differentiation and premature cell death during corticogenesi s. Our results indicate that the subplate neuron defects lead to the failur e of guidance and innervation of thalamocortical projections. Thus, our fin dings demonstrate a critical role of the subplate in early corticothalamic connectivity and confirm the importance of afferent innervation for the sur vival of layer IV neurons. These results also substantiate COUP-TFI as an i mportant regulator of neuronal development and differentiation.