TGFβ-Signaling and FOXG1-Expression Are a Hallmark of Astrocyte Lineage Diversity in the Murine Ventral and Dorsal Forebrain

WEISE, STEFAN CHRISTOPHER; VILLARREAL, ALEJANDRO; DEHGHANIAN, FARIBA; SCHACHTRUP, CHRISTIAN; SCHWARZ, JENNIFER; THEDIECK, KATHRIN; HEIDRICH, STEFANIE; NESTEL, SIGRUN; VOGEL, TANJA

Frontiers in Cellular Neuroscience

Frontiers

Año: 2018 vol. 12

Heterogeneous astrocyte populations are defined by diversity in cellular environment,progenitor identity or function. Yet, little is known about the extent of the heterogeneityand how this diversity is acquired during development. To investigate the impact of TGF(transforming growth factor) β-signaling on astrocyte development in the telencephalonwe deleted the TGFBR2 (transforming growth factor beta receptor 2) in early neuralprogenitor cells in mice using a FOXG1 (forkhead box G1)-driven CRE-recombinase.We used quantitative proteomics to characterize TGFBR2-deficient cells derived fromthe mouse telencephalon and identified differential protein expression of the astrocyteproteins GFAP (glial fibrillary acidic protein) and MFGE8 (milk fat globule-EGF factor 8).Biochemical and histological investigations revealed distinct populations of astrocytesin the dorsal and ventral telencephalon marked by GFAP or MFGE8 protein expression.The two subtypes differed in their response to TGFβ-signaling. Impaired TGFβ-signalingaffected numbers of GFAP astrocytes in the ventral telencephalon. In contrast, TGFβreduced MFGE8-expression in astrocytes deriving from both regions. Additionally,lineage tracing revealed that both GFAP and MFGE8 astrocyte subtypes derived partlyfrom FOXG1-expressing neural precursor cells.