Attenuated BDNF-induced upregulation of GABAergic markers in neurons lacking Xbp1

XBP1 is a transcription factor induced by unconventional splicing associated with endoplasmic reticulum stress and plays a role in development. Brain-derived neurotrophic factor (BDNF) causes splicing of Xbp1 mRNA in neurites, and Xbp1 is required for BDNF-induced neurite extension and branching. To search for the molecular mechanisms of how Xbp1 plays a role in neural development, comprehensive gene expression analysis was performed in primary telencephalic neurons obtained from Xbp1 knockout mice at embryonic day 12.5. By searching for the genes induced by BDNF in wild type neurons but not in Xbp1 knockout mice, we found that upregulation of three GABAergic markers, somatostatin (Sst), neuropeptide Y (Npy), and calbindin (Calb1), were compromised in Xbp1 knockout neurons. Attenuated upregulation of Npy and Calb1 in Xbp1 knockout neurons was confirmed by quantitative RT-PCR. This finding may be relevant to impaired BDNF-induced neurite extension in Xbp1 knockout neurons.