Mammalian cerebral cortex development
UNDERLYINING CELL FATE SPECIFICATION IN THE MAMALLIAN CEREBRAL CORTEX

Britanova O, Shcheglov A.
Collaborations: Abteilung fur Molekukare Biologie Neuronaler Signale
(Abteilungdirektor: Prof. Dr. Walter Stumer);
Max-Planck-Institut fur Experimentalle Medizin

The cerebral cortex is a tissue with a high degree of neuronal diversity. It consists of six cell layers with a unique set of neuronal subtypes. A crucial step in the process of cortical differentiation is the transition from a mitotically active neuroblast to a postmitotic young neuron. We used SSH-MOS combination and Ordered Differential Display method to identify genes involved in the control of this transition. Several genes that are differentially expressed during mouse cortical development were isolated, including PTTG, prc1, mouse homolog of the human putative transcription factor LAF4, and also a novel transcription factor that we named Stix.
During the stages E11.5-E13.5 PTTG and prc1 are expressed in most tissues of the embryo. Within the telencephalon, PTTG and prc1 are found exclusively inside of the ventricular zone (VZ). The intensity of the expression of both genes in the ventricular zone reaches its peak by E15.5. Expression starts to decrease by E18.5, it is still visible at least up to P2 and not detectable in the adult brains. Expression of the prc1 gene, but not that of the PTTG, is also found in the mitoticaly active cells outside of the VZ within the telencephalon. Most of the cells expressing the PTTG gene were found in the lower part of the ventricular zone suggesting that the level of PTTG mRNA is regulated during different phases of the mitotic cycle.
Several alternatively spliced forms of Laf4 were cloned from mouse. Two forms of are expressed during embryogenesis, whereas the other forms are expressed mainly in adults. We have found that Laf4 transcription becomes very quickly upregulated as soon as young cortical neurons leave the ventricular zone (VZ), the cortical-proliferative compartment. This coincides with the initial steps of cortical differentiation. Laf4 becomes downregulated in postnatal cortex, indicating its involvement in the transcriptional regulation of the early steps of cortical differentiation.
Stix is expressed in a cell type restricted manner in mouse embryo. Within the cerebral cortex it is expressed in the neurons of future superficial layers. We suppose that Stix is involved in the control of cell identity during development. Now we are going to investigate the biological role of Stix gene and its product during mouse development.