ABSTRACT
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.
Footnotes
Author contributions
Conceptualization: A.I., S.T.; Data curation: A.I., S.T., R.F., P.B., S.K., A.S., J.Z., R.B., R.N.; Formal analysis: A.I., R.F., P.B., A.S.; Funding acquisition: S.T., A.I.; Investigation: A.I., S.K.; Methodology: A.I., R.F., P.B., S.K.; Project administration: S.T., A.I.; Resources: S.T., A.I.; Supervision: S.T., A.I.; Validation: A.I.; Visualization: A.I., P.B.; Writing – original draft: A.I.; Writing – review & editing: S.T., A.I., R.F.
Funding
This work was funded by the Department of Science and Technology, Ministry of Science and Technology, India INSPIRE Faculty Fellowship awarded to A.I. (Faculty Registration number IFA18-LSBM210) and the Department of Atomic Energy, Government of India (Project Identification number RTI4003, DAE OM number 1303/2/2019/R&D-II/DAE/2079).
Data and resource availability
The Fastq files of the RNA-seq data generated from P3 sorted astrocytes for control and Lhx2 mutants have been deposited in the NCBI SRA with bioproject accession number PRJNA1149579.
Special Issue
This article is part of the Special Issue ‘Lifelong Development: the Maintenance, Regeneration and Plasticity of Tissues’, edited by Meritxell Huch and Mansi Srivastava. See related articles at https://journals.biologists.com/dev/issue/152/20.
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