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FOXG1 syndrome is a developmental encephalopathy caused by FOXG1 (Forkhead box G1) mutations, resulting in high phenotypic variability. However, the upstream transcriptional regulation of Foxg1 expression remains unclear. This report demonstrates that both deficiency and overexpression of Men1 (protein: menin, a pathogenic gene of MEN1 syndrome known as multiple endocrine neoplasia type 1) lead to autism‐like behaviors, such as social defects, increased repetitive behaviors, and cognitive impairments. Multifaceted transcriptome analyses revealed that Foxg1 signaling is predominantly altered in Men1 deficiency mice, through its regulation of the Alpha Thalassemia/Mental Retardation Syndrome X‐Linked (Atrx) factor. Atrx recruits menin to bind to the transcriptional start region of Foxg1 and mediates the regulation of Foxg1 expression by H3K4me3 (Trimethylation of histone H3 lysine 4) modification. The deficits observed in menin deficient mice are rescued by the over‐expression of Foxg1, leading to normalized spine growth and restoration of hippocampal synaptic plasticity. These findings suggest that menin may have a putative role in the maintenance of Foxg1 expression, highlighting menin signaling as a potential therapeutic target for Foxg1‐related encephalopathy. [ABSTRACT FROM AUTHOR]

Micro/nanotextured topographies (MNTs) can modulate cell-biomaterial interactions mostly by their controllable geometrics. Among them, TiO 2 nanotubes, regarded as having a highly controllable nanoscale geometry, have been extensively investigated and applied and significantly affect diameter-dependent cell biological behaviors. In this study, we used five typical MNTs decorated with TiO 2 nanotubes with diameters of 30, 50, 70, 100 and 120 nm to explore the optimal nanotube diameter for improving the biofunctional properties and to more deeply understand the underlying mechanisms by which these MNTs affect osteogenic differentiation by revealing the effect of beta1-integrin/Hedgehog-Gli1 signaling on this process. The MNTs affected MG63 osteoblast-like cell spreading, osteogenic gene expression (BMP-2, Runx2 and ALP), mineralization and ALP activity in a diameter-dependent pattern, and the optimal TiO 2 nanotube diameter of 70 nm provided the best microenvironment for osteogenic differentiation as well as beta1-integrin/Hedgehog-Gli1 signaling activation. This enhanced osteogenic differentiation by the optimal-diameter TiO 2 nanotubes of 70 nm was attenuated via suppression of the beta1-integrin/ Hedgehog-Gli1 signaling, which indicated a significant role of this pathway in mediating the diameter-dependent osteogenic differentiation promotional effect of MNTs with different TiO 2 nanotube diameters. These results might provide deeper insights into the signal transduction mechanisms by which different nanoscale geometries influence cellular functions for biomaterial modification and biofunctionalization., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)