Astrocyte morphogenesis is dependent on BDNF signaling via astrocytic TrkB.T1

Astrocytic morphogenesis and maturation are critical steps in CNS development. The time window of astrocyte morphological development is well defined, but the molecular underpinnings are still unclear. BDNF is a critical growth factor involved in the development of the CNS, including synapse refinement. Here we demonstrate the BDNF receptor at Ntrk2 is enriched in astrocytes relative to all CNS cell populations. RNA sequencing indicates Ntrk2 falls in the top 0.001% of all gene transcripts expressed in juvenile astrocytes, almost exclusively due to truncated TrkB.T1. Astrocyte complexity is increased in the presence of BNDF in vitro, which is dependent upon the presence of TrkB.T1. Furthermore, deletion of TrkB.T1 in vivo revealed astrocytes with significantly reduced volume and branching complexities. Indicating a role for functional astrocyte maturation via BDNF/TrkB.T1 signaling, TrkB.T1 KO astrocytes do not support normal excitatory synaptogenesis. Together, these data suggest a significant role for BDNF/TrkB.T1 signaling in astrocyte morphogenesis and indicate this signaling may contribute to astrocyte regulation of neuronal synapse development. Overall design: Wild-type (WT) males were bred with heterozygous Mecp2tm1.1Jae/+ (Jaenisch) female mice. Astrocytes were acutely isolated from whole cortex as previously described (Holt and Olsen, 2016)) from WT males ranging from postnatal days 25-31. An n of 5 biological replicates were used. For RNA-Sequencing, 2 technical replicates were run per biological replicate.