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Trnp1 Regulates Expansion of Cerebral Cortex

During the fetal development of many mammals the cerebral cortex increases in size and becomes folded. Scientists of Helmholtz
Zentrum München have now succeeded in identifying the key protein responsible for this process.

Different brain regions have different tasks and must be specifically expanded as required. In the forebrain of mammals, the cerebral cortex – which is responsible for cognitive function – is usually highly folded and expanded. The more folds and wrinkles there are, the larger the surface and the better the brain can absorb and process information. In humans, the brain surface of the fetus is mostly smooth until approximately the sixth month of pregnancy; it is not until after this that the folding begins.

Until this study, it was completely unknown which mechanisms trigger the expansion and folding of the brain in the course of fetal development. Now for the first time, Magdalena Götz and her team have identified the corresponding molecular mechanism in the mouse model: The responsible protein is the nuclear protein Trnp1, whose dynamic regulation triggers an enormous proliferation of neurons of the cerebral cortex and stimulates folding even in mice that normally exhibit smooth, unfolded brains. Trnp1 is thus a key protein for the expansion and folding of the cerebral cortex.

During fetal development it is dynamically controlled: In the early phases of development Trnp1 levels are high. This favors the formation of radial glial cells, and specific brain regions expand. Later, Trnp1 levels drop again to lower levels. As a consequence, the formation of various progenitor cells and glial cells is stimulated, and a particularly large number of newly formed neurons arrange themselves in a folded structure.

This molecular mechanism is particularly interesting because both the expansion and the folding of the brain are regulated by the same molecule – Trnp1. Thus, Trnp1 represents a very promising approach for investigation of the cellular and molecular mechanisms underlying these complex processes – an approach that Götz and her team want to pursue further.

The cerebral cortex is the neuron-rich outer layer of the cerebrum. Depending on the region, it is only two to five ­millimeters thick and is part of the gray matter of the cerebrum. The nerve fibers of the neurons of the cerebral cortex extend below the cortex and form the white matter of the cerebrum that consists largely of myelin­ated nerve fibers bundled into tracts.