形態形成セミナー Robert F. Hevner先生




日時:11月30日(月)午後5時から6時半
場所:総合医科学研究棟一階ラウンジ

『T-box Transcription Factors in Cortical Neurogenesis and the Response to Injury』

          Robert F. Hevner

            Professor
            Neurological Surgery and Pathology, University of Washington

In previous studies, we have found that glutamatergic neurogenesis in the embryonic cerebral cortex, as well as the adult hippocampus and developing cerebellum, involves a conserved transcription factor (TF) cascade from Pax6 to Tbr2 to Tbr1 in stem-like progenitors, intermediate neuronal progenitors (INPs) and postmitotic neurons, respectively. More recently, we were surprised to observe Tbr2 expression in progenitor cells of the adult subependymal zone (SEZ) and rostral migratory stream (RMS), regions thought to produce only GABAergic neurons for the olfactory bulb. To determine if Tbr2 was expressed in the GABAergic progenitors, we examined a variety of lineage markers in relation to Tbr2. Unexpectedly, we found that Tbr2 was expressed in a novel subset of progenitors distinct from the GABAergic lineage, and instead contributing to adult neurogenesis of Tbr1+ glutamatergic periglomerular neurons in the adult olfactorybulb. Moreover, under experimental conditions of induced ischemic stroke or neuronal photo ablation, Tbr2+ progenitors and daughter cells were recruited from the SEZ into the cerebral cortex, where they differentiated into Doublecortin (DCX) expressing neuroblasts, potentially providing a source of new pyramidal neurons. These findings indicate that: (1) In all regions studied so far, Tbr2+ progenitors in diverse brain areas and ages produce only glutamatergic, and not GABAergic neurons; (2) adult neurogenesis in the SEZ-RMS-olfactory bulb system includes a minority (5-15%) glutamatergic lineage, unrecognized in prior studies; and (3) Tbr2+ SEZ progenitors may account for previous observations of pyramidal neuron production in the adult cerebral cortex, and may provide an important source of glutamatergic neurons for therapeutic purposes.

連絡先:仲嶋一範(慶應医・解剖学) phone: 03-3353-1211 内線62601 e-mail: kazunori
参加自由
共催:グローバルCOEプログラム『In vivoヒト代謝システム生物学拠点』