Abstract

The forebrain is generated by distinct sets of precursor cells that express specific transcription factors as well as secreted signaling factors in a time- and region-dependent manner. The distribution of these factors is similar in the avian and mammalian forebrains. In this work I aimed to examine the molecular mechanisms regulating telencephalic patterning. Therefore, I first compared the expression pattern of homeobox transcription factors, known to play crucial roles in regionalization of the forebrain, such as Emx1 and Emx2. This analysis showed particularly intriguing domains in the developing telencephalon expressing either only Emx2, such as the dorso-ventricular ridge (DVR) and the cortical hem, both genes, such as the hippocampus and the pallium or none, such as the subpallium and the choroid plexus (ChP). Taken together with other expression patterns I could conclude that the DVR, the nature of which was debated for a long period of time, displays a dorsal nature and that the pallial/subpallial boundary is located between DVR and subpallium. Next, I aimed to examine the role of Emx1 and Emx2 in the specification of these distinct regions. Therefore, I used a misexpression approach targeting Emx1 and Emx2 into the anlage of the choroid plexus (ChP) where these transcription factors are normally not expressed. In this region normal development was disturbed. The normally non-neuronal, thin morphology of the ChP with a low rate of proliferation and the characteristic expression of Otx2 and Bmp7 was lost. Instead, the rate of proliferation and the thickness of the tissue were increased and rather displayed “hem-like” properties. Instead, the Otx2-positive region of the ChP was shifted beside the region of ectopic Emx1/2-expression and exhibited intermediate properties, with features of ChP-tissue like Otx2 and Bmp7-expression, but also features of the cortical hem with a higher rate of proliferation and increased thickness of tissue. Thus, Emx1 and Emx2 play a key role in instructing dorsal neuroepithelium to proliferate. The misexpression of these genes is sufficient to convert non-neuronal ChP-tissue into neuroepithelium. Ectopic expression of Emx1/2 in the dorsal pallium, its normal region of expression, also displayed alterations. Ectopic Emx-expression blocked the expression of the neurogenic transcription factor Pax6 and suppressed neuronal differentiation. This change of neuronal differentiation could be caused by reduction of Pax6. Taken together, Emx1 and Emx2 are two potent factors that can change regional identity, enhance proliferation and block neuronal differentiation.