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In pluricellular organisms, cell differentiation helps to decrease the total amount of energy needed for life. These differentiations can be evidenced at the tissular, the cellular or the molecular levels. Cell differentiation is a progressive process achieved during embryogenesis; different steps in the program can be described. One of the explanations to account for cell differentiation is the specific expression of proteins, called transcription factors, that can control the expression of selected genes. These factors are classified according to their biochemical pattern allowing description of several families of transcription factors. One of the salient questions during embryogenesis is to understand the mechanisms involved in cell differentiation. The first event is due to asymmetry of mitosis leading to the generation of two cell lineages. This is favored by the initial ovocyte polarization. The second event is due to cell interactions (namely inductions). These inductions may be explained either by cell-cell contact (favored by cell adhesion molecules) or by secreting factors that can be either hydrophilic or lipophilic.

Stem-cells have been identified in the adult human brain in two zones which are the subventricular zone and the gyrus dentatus of the hippocampus. Improvement of techniques aimed to identify, to localize and to follow the lineage of these cells have been crucial to the understanding of the following processes: a) identification of cellular proliferation, b) specific immunostaining of differentiated glial and neuronal cells, c) transplantations to decipher between intrinsic stem-cell properties and influence of the environment on the fate of the cell. Furthermore, it seems that stem-cells from other sources than the brain can differentiate into neurons both in vitro and in vivo. The aim of this review is to sum up what is known about cerebral stem-cells and the challenging tools they mean for the future.

Understanding how the cortex develops has gained very important new data thanks to both experimental and clinical studies. Experimental studies have shown that: --neurons are generated in the ventricular zone by asymmetric mitoses; --the first cortical region to differentiate is the so-called pre-plate that plays a major role in the control of neuroblasts migration; --neuroblasts arise according to an inside-outside gradient; they migrate either along the processes of radial cells or according to a new type of non radial migration; --all the cortical neurons are not generated by the dorsal telencephalon; some of these neurons derive from the basal telencephalon; --neuroblasts acquire their specificity during their way to the cortical plate. There are several genetic syndromes leading to a malformation of the cortex. Classic lissencephaly is essentially due to mutations of the LIS1 or the DCX genes. These genes code for proteins that are involved in cytoskeleton functions. Reelin is responsible for a human syndrome associating pachygyria and cerebellar hypotrophy. Subventricular heterotopia can be X- inherited and are due to a mutation of the gene coding for filamin 1.

The corpus callosum is the most important cerebral commissure allowing axonal fibres to cross the midline. Corpus callosum agenesis is an important condition in man that can reveal numerous genetic syndromes. The corpus callosum develops from the commissural plate, a dorsal region of the telencephalon. Then, axons growing from pyramidal neurons of cortical layer III extend and cross the midline. In experimental models, it is possible to decipher two conditions in which the development of the corpus callosum is impaired. The first condition is characterized by an impairment of the formation of the roof of the telencephalon (the primordium of the commissural plate). This condition can be explained by an abortive induction of this region by an impairment of BMP signaling. This can generate all the forms of holoprosencephaly. Other forms are due to a defective gene coding Hesx1, a transcription factor involved in the control of telencephalic morphogenesis. Such a genetic defect can be observed in human dominant forms of septo-optic dysplasia. The second condition is explained by an impairment of the molecular control of axon growth: such is the case for the couple netrin 1 and DCC or for the adhesion molecule L1.