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At the onset of mammalian neurogenesis, neuroepithelial (NE) cells switch from proliferative to neuron-generating divisions. Understanding the molecular basis of this switch requires the ability to distinguish between these two types of division. Here we show that in the mouse ventricular zone, expression of the mRNA of the antiproliferative gene TIS21 (PC3, BTG2) ( i ) starts at the onset of neurogenesis, ( ii ) is confined to a subpopulation of NE cells that increases in correlation with the progression of neurogenesis, and ( iii ) is not detected in newborn neurons. Expression of the TIS21 mRNA in the NE cells occurs transiently during the cell cycle, i.e., in the G 1 phase. In contrast to the TIS21 mRNA, the TIS21 protein persists through the division of NE cells and is inherited by the neurons, where it remains detectable during neuronal migration and the initial phase of differentiation. Our observations indicate that the TIS21 gene is specifically expressed in those NE cells that, at their next division, will generate postmitotic neurons, but not in proliferating NE cells. Using TIS21 as a marker, we find that the switch from proliferative to neuron-generating divisions is initiated in single NE cells rather than in synchronized neighboring cells.

PC4 is an early NGF-inducible gene, transiently expressed during the in vitro differentiation of PC12 cells toward a neuronal phenotype. By in situ hibridization analysis, we found that PC4 is expressed at high levels along the whole neural tube of early rat embryos. PC4 mRNA expression is not uniform across the wall of the neural tube, the autoradiographic signal being most intense on the ventricular layer. At later stages, when the rate of proliferation and production of postmitotic neurons decreases, PC4 gene expression also decreases and becomes restricted to the telencephalon, that is the last region to complete neurogenesis. Thus the expression of PC4 gene, although not exclusive of proliferating cells, appears to be correlated to the time span of proliferation of neuronal and glial precursors.

Planarians (Platyhelminthes) possess an abundant population of adult stem cells, the neoblasts, capable to give rise to both somatic and germ cells. Although neoblasts share similar morphological features, several pieces of evidence suggest that they constitute a heterogeneous population of cells with distinct ultrastructural and molecular features. We found that in planarians treated with low X-ray doses (5 Gy), only a few neoblasts survive. Among these cells, those located close to the nervous system activate an intense proliferation program and migrate to reconstitute the whole complex neoblast population. This phenomenon is inhibited by the substance P receptor antagonist spantide, and accompanied by the up-regulation of a number of genes implicated in neuronal signalling and plasticity, suggesting that signals of neural origin modulate neoblast proliferation and/or migration. Here, we review these findings and the literature available on the influence of the nervous system on stem cell activity, both in planarians and vertebrates, and we propose 5 Gy-treated planarians as a unique model system to study the influence of neural signalling on stem cell biology.

CHARGE syndrome is an autosomal dominant disorder characterized by features represented in its acronym: Coloboma, Heart defect, Atresia of the choanae, Retarded growth and development, Genital abnormalities, Ear anomalies/deafness. We report two patients with a diagnosis of typical CHARGE syndrome and one with atypical clinical diagnosis. All the three patients had uni- or bilateral choanal atresia and sensorineural hearing loss. The patients were screened for CHD7 gene mutations. Three novel occurring de novo heterozygous mutations were identified: a mutation in the donor splice site of intron 24, a missense mutation in exon 2 and a deletion in exon 11.

We examined the developmental expression of PC3, a nerve growth factor (NGF) early induced gene in PC12 cells, in the rat central nervous system (CNS) and we found that it represents a molecular marker of ongoing postmitotic neurons production. PC3 is initially expressed in the ventral quarter of the neural tube, at the level of the presumptive cervical spinal cord just where and when (10–11 days post coitum (dpc)) the motor neurons are arising. Subsequently, the appearance of PC3 expression follows a ventro-dorsal and a rosto-caudal gradient in the spinal cord and a caudo-rostal gradient across the brain vesicles that coincide, both spatially and temporally, with the gradients of neurogenesis described in the literature. As in PC12 cells, PC3 mRNA expression appears to be transient in vivo. In all regions of the CNS, it is restricted to the ventricular zone of the neuroepithelium, while neuronal precursors cease to express PC3 as they migrate to the mantle zone. Moreover, PC3 mRNA disappears from the various regions of the CNS as neurogenesis ceases.