The transcription factor LHX2 suppresses astrocyte proliferation in the postnatal mammalian cerebral cortex

In the developing cerebral cortex, astrocytes arise from progenitors in the ventricular and subventricular zones (V-SVZ), and also from local proliferation within the parenchyma. In the mouse neocortex, astrocytes that occupy upper layers (UL) versus deep layers (DL) are known to be distinct populations in terms of molecular and morphological features. The transcription factor LHX2 is expressed both in V-SVZ gliogenic progenitors and in differentiated astrocytes throughout development and into adulthood. Here, we show that loss of Lhx2 at birth results in an increased astrocyte proliferation in the UL but not the DL of the cortex in the first postnatal week. Consistent with this, transcriptomic signatures of UL astrocytes increase. By 3 months, Lhx2 mutant astrocytes display upregulation of GFAP, and transcriptomic signatures associated with 'reactive' astrocytes, in the absence of injury. These results demonstrate a role for Lhx2 in regulating proliferation and molecular features of cortical astrocytes.