LHX2 regulates dendritic morphogenesis in layer II/III neurons of the neocortex.

Abstract

In the mammalian neocortex, the two hemispheres communicate via the corpus callosum. We investigated mechanisms regulating dendritic arbors and spines of callosal neurons. The transcription factor LIM Homeodomain 2 (<i>Lhx2</i>), a key regulator of cortical development, is expressed in postmitotic layer II/III neurons and their progenitors. Loss of <i>Lhx2</i> in either population caused similar but distinct phenotypes: reduced dendritic arbors, altered spine morphology, and changed electrophysiological properties. Morphometric defects were more severe when <i>Lhx2</i> was disrupted in progenitors and were recapitulated by its specific loss in basal progenitors. <i>Lhx2</i> loss in progenitors aberrantly up-regulated <i>Neurog2</i> in postmitotic neurons, and <i>Neurog2</i> knockdown partially rescued the phenotype. Loss of <i>Lhx2</i> at either stage also up-regulated Wnt signaling pathway genes. The mutant phenotype was mimicked by constitutive activation of β-CATENIN in postmitotic neurons. Our findings reveal previously unidentified LHX2-dependent mechanisms of dendritic morphogenesis, highlighting its temporally dynamic and diverse roles in neocortical development.