TGFβ-signalling and FOXG1 expression hallmark astrocyte lineage diversity in the murine ventral and dorsal forebrain

Heterogeneous astrocyte populations are defined by diversity in cellular environment, progenitor identity or function. Yet, little is known about the extent of the heterogeneity and how this diversity is acquired during development. We used SILAC and quantitative proteomics to characterise primary murine telencephalic progenitor cells from FOXG1 (forkhead box G1)-cre driven Tgfbr2 (transforming growth factor beta receptor 2) knockout mice and identified differential protein expression of the astrocyte proteins GFAP (glial fibrillary acidic protein) and MFGE8 (milk fat globule-EGF factor 8). Biochemical and histological investigations revealed distinct populations of astrocytes in the dorsal and ventral telencephalon marked by GFAP or MFGE8 protein expression. The two subtypes differed in their response to TGFβ-signalling. Impaired TGFβ-signalling affected numbers of GFAP-astrocytes in the ventral telencephalon. In contrast, TGFβ reduced MFGE8 expression in astrocytes deriving from both regions. Additionally, lineage tracing revealed that both GFAP and MFGE8 astrocyte subtypes derived partly from FOXG1-expressing neural precursor cells.