Clinical Significance
TBR1 has been implicated in alterations in the brain that may lead to Alzheimer’s Disease (AD) and Parkinson’s Disease (PD). TBR1 expressing mice showed that cholinergic neurons of the basal forebrain (ChBF), the degeneration of which are involved in the development of AD and PD, migrate from the ventral pallium to the subpallium. This was confirmed using TBR1 null mice. In the future, the researchers plan to explore the role of amyloid precursor protein (APP) in neuronal migration and linkage to these diseases.
Reduced function of NMDA receptors play a role in schizophrenia. This diminished function of NMDA receptor may be correlated with the reduced expression of the NMDA receptor 2B subunit (NR2b), which has also been linked to schizophrenia. TBR1, in complex with the protein, CINAP, is responsible for regulating transcription of the NR2b gene. It was hypothesized in one 2010 study that reduced TBR1 and CINAP expression may be responsible for the reduced expression of the NR2b subunit observed in brains of postmortem schizophrenics. However, TBR1 and CINAP expression were not significantly reduced in the postmortem brains, suggesting that synthesis and processing of NR2b via TBR1 is not responsible for reduced NR2b expression in schizophrenics.
TBR1 expression has been shown to be downregulated by embryonic exposure to cocaine. Prenatal cocaine exposure in a mouse model caused a decrease in both GABA neuron migration from the basal to the dorsal forebrain and radial neuron migration in the dorsal forebrain. This exposure also decreased TBR1 and TBR2 expression. However, further research showed that cocaine exposure only delayed TBR1 expression and did not cause permanent downregulation. Therefore in models of prenatal cocaine exposure both migration and maturation of these progenitor cells is delayed.
TBR1 is also used in immunohistochemical techniques in neurological research. It has been used to identify layer VI developing cortical neurons as well as the prethalamic eminence, pallium, and dorsal forebrain. The presence of TBR1 in stem cells responding to telencephalon injury implicates the normal function of these cells in this region of the brain.
Mutations of this gene have also been associated with medulloblastoma.
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