LHX2 regulates dendritic morphogenesis in layer II/III of the neocortex via distinct pathways in progenitors and postmitotic neurons

Abstract

AbstractIn the mammalian neocortex, excitatory neurons that send projections via the corpus callosum are critical to integrating information across the two brain hemispheres. The molecular mechanisms governing the development of the dendritic arbours and spines of these callosal neurons are poorly understood, yet these features are critical to their physiological properties. LIM Homeodomain 2 (Lhx2), a regulator of fundamental processes in cortical development, is expressed in postmitotic callosal neurons occupying layer II/III of the neocortex and also in their progenitors in the embryonic day (E) 15.5 ventricular zone of the mouse neocortex. We tested whether this factor is essential for dendritic arbour configuration and spine morphogenesis of layer II/III neurons. Here, we report loss ofLhx2either in postmitotic callosal neurons or their progenitors, resulting in shrunken dendritic arbours and perturbed spine morphology. In postmitotic neurons, we identified that LHX2 regulates dendritic and spine morphogenesis via the canonical Wnt/β Catenin signalling pathway. Constitutive activation of this pathway in postmitotic neurons recapitulates theLhx2loss-of-function phenotype. In E15.5 progenitors, we identified that bHLH transcription factorNeurog2mediates LHX2 function in regulating dendritic and spine morphogenesis. We show thatNeurog2expression increases upon loss ofLhx2and that shRNA-mediatedNeurog2knockdown rescues the loss ofLhx2phenotype. Our study uncovers novel LHX2 functions in cortical circuit assembly consistent with its temporally dynamic and multifunctional roles in development.