A novel murine and human gene, TBR-1, encodes a putative transcription factor related to the Brachyrury (T) gene that is expressed only in postmitotic cells. T-brain-1 (TBR-1) mRNA is largely restricted to the cerebral cortex, where, during embryogenesis, it defines different regions that give rise to the palecortex, limbic cortex and neocortex. TBR-1, Pax-6 and Emx-1 are expressed in the mouse and chicken pallium. The pallio-subpallial boundary lies at the interface between the TBR-1 and Dlx-2 expression domains. Chicken genes homolgous to these mouse genes are expressed in topologically comparable patterns during development, suggesting that mouse and chicken may have similar histogenetic specification processes and field homologies. CASK/LIN-2, a membrane-associated guanylate kinase, is required for EGFR localization and signaling. In adult rat brain, CASK is concentrated at neuronal synapses and binds to the cell-surface proteins. CASK can interact with TBR-1, which is involved in forebrain development. CASK enters into the nucleus and binds to a specific DNA sequence (the T-element) in a complex with TBR-1. Thus, CASK acts as a coactivator of TBR-1 to induce transcription of T-element containing genes, including reelin.