Tbr-1 mRNA expression in the developing human cerebral cortex

M. Molnar; C.R. Neal; E.G. Jones
Society for Neuroscience 34th Annual Meeting. 2004.


Tbr1- is a transcription factor expressed in glutamatergic neurons in the developing and adult cortex. Mutation studies in mice show that Tbr-1 plays important roles during development, being involved in cortical neuronal migration and in the establishment of cortical connections. Our preliminary findings suggest an involvement of Tbr-1 in schizophrenia. Specifically we found a trend toward a down regulation of Tbr-1 mRNA expression in the prefrontal cortex of schizophrenic patients, with the largest effect in layer III. The expression of Tbr-1 during cortical development is well documented in mice and other species including chicks, and Xenopus, but has not been assessed in the developing human cortex. In the present study we investigated the expression of Tbr-1 mRNA in the developing human cortex using standard isotopic in situ hybridization techniques. Embryonic human brains were used from 16, 21, 22 and 35 weeks old embryos. All embryos were screened for chromosomal abnormalities. Hybridization signal was detected in the cortical plate as early as 16 weeks of gestation. In 21 and 22 weeks old embryos labeled neurons were mainly present in layers V and VI. At 35 weeks, labeling is still mainly present in layers V and VI. In addition, few strongly labeled cells start to be detected in layer II. In the adult human cortex Tbr-1 mRNA is expressed mainly in layer VI, layer II, deep layer III. Since at 35 weeks of gestation all the six cortical layers are present in the human cortex, our results suggest a postnatal regulation of Tbr-1 mRNA expression. This implies that Tbr-1 in human is possibly involved in both prenatal and postnatal cortical development. In addition they suggest that potentially, a defective postnatal development of layer III is present in schizophrenia. Supported by grants MH54844 and MH60398 from HIMH and by Pritzker Neuropsychiatric Disorders Research Consortium.