TY - JOUR AU - Vinci, Ersilia AU - Beretta, Stefania AU - Colombo, Veronica AU - Zippo, Antonio AU - Catanese, Alberto AU - Wiegreffe, Christoph AU - Britsch, Stefan AU - Boeckers, Tobias AU - Verpelli, Chiara AU - Sala, Carlo TI - Regulation of Dendrite and Dendritic Spine Formation by TCF20. JO - Journal of neurochemistry VL - 169 IS - 1 SN - 0022-3042 CY - Oxford PB - Wiley-Blackwell M1 - DZNE-2025-00120 SP - e16297 PY - 2025 AB - Mutations in the Transcription Factor 20 (TCF20) have been identified in patients with autism spectrum disorders (ASDs), intellectual disabilities (IDs), and other neurological issues. Recently, a new syndrome called TCF20-associated neurodevelopmental disorders (TAND) has been described, with specific clinical features. While TCF20's role in the neurogenesis of mouse embryos has been reported, little is known about its molecular function in neurons. In this study, we demonstrate that TCF20 is expressed in all analyzed brain regions in mice, and its expression increases during brain development but decreases in muscle tissue. Our findings suggest that TCF20 plays a central role in dendritic arborization and dendritic spine formation processes. RNA sequencing analysis revealed a downregulation of pre- and postsynaptic pathways in TCF20 knockdown neurons. We also found decreased levels of GABRA1, BDNF, PSD-95, and c-Fos in total homogenates and in synaptosomal preparations of knockdown TCF20 rat cortical cultures. Furthermore, synaptosomal preparations of knockdown TCF20 rat cortical cultures showed significant downregulation of GluN2B and GABRA5, while GluA2 was significantly upregulated. Overall, our data suggest that TCF20 plays an essential role in neuronal development and function by modulating the expression of proteins involved in dendrite and synapse formation and function. KW - Animals KW - Dendritic Spines: metabolism KW - Dendrites: metabolism KW - Mice KW - Rats KW - Cells, Cultured KW - Male KW - Mice, Inbred C57BL KW - Neurogenesis: physiology KW - Female KW - BDNF (Other) KW - dendritic spines (Other) KW - nruodevelopmental disease (Other) KW - synapses (Other) LB - PUB:(DE-HGF)16 C2 - pmc:PMC11725998 C6 - pmid:39801227 DO - DOI:10.1111/jnc.16297 UR - https://pub.dzne.de/record/275885 ER -