TBR1

Last update 08 May 2025

Basic Info

Synonyms

T-box brain protein 1, T-box brain transcription factor 1, T-brain-1

+ [3]

Introduction

Transcriptional repressor involved in multiple aspects of cortical development, including neuronal migration, laminar and areal identity, and axonal projection (PubMed:25232744, PubMed:30250039). As transcriptional repressor of FEZF2, it blocks the formation of the corticospinal (CS) tract from layer 6 projection neurons, thereby restricting the origin of CS axons specifically to layer 5 neurons (By similarity).

100 Clinical Results associated with TBR1

100 Translational Medicine associated with TBR1

0 Patents (Medical) associated with TBR1

350

Literatures (Medical) associated with TBR1

01 Apr 2025·The Ocular Surface

Smad4 deficiency ameliorates the progressive corneal stroma thinning caused by the loss of Tbr1

Article

Author: Yuan, Yong ; Funk, Kaitlyn L ; Saika, Shizuya ; Kao, Winston ; Kaufman, Adam ; Liu, Chia-Yang ; Yasuda, Shingo

PURPOSETo understand how Tbr1 and Smad4 play a pivotal role in controlling ECM synthesis versus degradation for maintaining corneal stromal homeostasis and otherwise leading to corneal ectasia.METHODSKeratocyte-specific and inducible knockout (iKO) of Tbr1, Smad4, or Tbr1/Smad4 double KO (iDKO) mice were generated. OCT was used to assess corneal thickness in vivo. Masson's trichrome and collagen hybridizing peptide stainings were performed to examine collagen expression. Immunostaining with an anti-cathepsin B antibody was used to assess ECM degradation. Cathepsin B inhibitor, CA-074Me, eyedrop was conducted to test its effect on treating stromal thinning in Tbr1 iKO mice.RESULTSTbr1 iKO and Smad4 iKO displayed corneal thinning, but Tbr1 iKO revealed a progressive and more severe pathology than Smad4 iKO. Tbr1 iKO cornea lost most of its stroma and thus a dome shape. Collagen ECM is evenly distributed in Smad4 iKO as well as control littermates but was lost mainly in the anterior stroma of the Tbr1 iKO. Interestingly, Tbr1/Smad4 iDKO ameliorated Tbr1 iKO phenotype. The basal level of Cathepsin b (Ctsb) could be detected in the control stroma but was significantly increased in the Tbr1 iKO stromal cells and this effect was canceled in Tbr1/Smad4 iDKO. CA-074Me eyedrops administration significantly inhibited progressive corneal thinning caused by the Tbr1 iKO.CONCLUSIONOur data from Tbr1/Smad4 iDKO argued that Smad4 played a pivotal role in controlling Tbr1-dependent ECM synthesis and Tbr1-independent ECM degradation to maintain corneal stromal integrity and homeostasis.

17 Feb 2025·Microscopy and Microanalysis

Structural Analysis of Cerebral Organoids Using Confocal Microscopy and Transmission/Scanning Electron Microscopy

Article

Author: Noh, Seulgi ; Kim, Beomsue ; Mun, Ji Young ; Park, Yurim

AbstractCerebral organoid cultures from human-induced pluripotent stem cells are widely used to study complex human brain development; however, there is still limited ultrastructural information regarding the development. In this study, we examined the structural details of cerebral organoids using various microscopy techniques. Two protocols were chosen as representative methods for the development of brain organoids: the classic whole-cerebral organoid (Whole-CO) culture technique, and the air–liquid interface-cerebral organoid (ALI-CO) culture technique. Immunostained confocal laser scanning microscopy (CLSM) revealed the formation of the CTIP2- and TBR1-positive cortical deep layer on days 90 and 150, depending on the developmental progress of both methods. Furthermore, the presence of astrocytes and oligodendrocytes was verified through immunostained CLSM utilizing two-dimensional and three-dimensional reconstruction images after a 150-day period. Transmission electron microscopy analysis revealed nanometer-resolution details of the cellular organelles and neuron-specific structures including synapses and myelin. Large-area scanning electron microscopy confirmed the well-developed neuronal connectivity from each culture method on day 150. Using those microscopy techniques, we clearly showed significant details within two representative culture protocols, the Whole-CO and ALI-CO culture methods. These multi-level images provide ultrastructural insight into the features of cerebral organoids depending on the developmental stage.

01 Jan 2025·Biological Psychiatry Global Open Science

GABA/Glutamate Neuron Differentiation Imbalance and Increased AKT/mTOR Signaling in CNTNAP2−/− Cerebral Organoids

Article

Author: Gkogkas, Christos G ; Samiotaki, Martina ; Moschovas, Dimitrios ; Voudouri, Georgia ; Avgeropoulos, Apostolos ; Zafeiri, Maria ; Statoulla, Elpida ; Chalkiadaki, Kleanthi ; Amvrosiadis, Theoklitos ; Theodoridou, Niki ; Typou, Alexandra ; Mason, John O

BackgroundThe polygenic nature of autism spectrum disorder (ASD) requires the identification of converging genetic pathways during early development to elucidate its complexity and varied manifestations.MethodsWe developed a human cerebral organoid model from induced pluripotent stem cells with targeted genome editing to abolish protein expression of the CNTNAP2 ASD risk gene.ResultsCNTNAP2^-/- cerebral organoids displayed accelerated cell cycle, ventricular zone disorganization, and increased cortical folding. Proteomic analysis revealed disruptions in glutamatergic/GABAergic (gamma-aminobutyric acidergic) synaptic pathways and neurodevelopment, and transcriptomic analysis revealed differentially expressed genes belonging to inhibitory neuron-related gene networks. Interestingly, there was a weak correlation between the 2 datasets, suggesting nuanced translational control mechanisms. Along these lines, we found upregulated AKT/mTOR (mechanistic target of rapamycin) signaling in CNTNAP2^-/- organoids. Spatial transcriptomic analysis of CNTNAP2^-/- ventricular-like zones demonstrated pervasive changes in gene expression, implicating upregulation of cell cycle regulation, synaptic, and glutamatergic/GABAergic pathways. We noted significant overlap of all day-30 organoid omics datasets differentially expressed genes from idiopathic ASD (macrocephaly) induced pluripotent stem cell-derived telencephalic organoids, where FOXG1 was upregulated. Moreover, we detected increased GAD1-expressing and decreased TBR1-expressing cells, suggesting altered GABAergic/glutamatergic neuron development.ConclusionsThese findings potentially highlight a shared mechanism in the early cortical development of various forms of ASD, further elucidate the role of CNTNAP2 in ASD pathophysiology and cortical development, and pave the way for targeted therapies that use cerebral organoids as preclinical models.

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TBR1

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