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Coni S.,Institute Of Biologie Valrose | Infante P.,Italian Institute of Technology | Gulino A.,Italian Institute of Technology | Gulino A.,University of Rome La Sapienza | Gulino A.,Neuromed Institute
Biochemical Pharmacology | Year: 2013

Hedgehog is a key morphogen regulating embryonic development and tissue repair. Remarkably, when misregulated, it leads to tumorigenesis. Hedgehog signaling is triggered by binding of ligands with transmembrane receptor Ptch and is subsequently mediated by transcriptional effectors belonging to the Gli family, whose functions is tuned by a number of molecular interactions and post-synthetic modifications. The complex of these regulatory circuitries provides a tight control of developmental processes, mainly involving the modulation of genes determining the fate of stem cells. Similarly, Hedgehog regulates cancer stem cells fostering tumorigenesis. To this regard, these processes represent promising targets for novel therapeutic strategies aiming at the control of stemness reactivation and maintenance in cancer. © 2012 Elsevier Inc.

Harb K.,University of Nice Sophia Antipolis | Harb K.,Institute Of Biologie Valrose | Harb K.,French National Center for Scientific Research | Magrinelli E.,University of Nice Sophia Antipolis | And 25 more authors.
eLife | Year: 2016

During cortical development, the identity of major classes of long-distance projection neurons is established by the expression of molecular determinants, which become gradually restricted and mutually exclusive. However, the mechanisms by which projection neurons acquire their final properties during postnatal stages are still poorly understood. In this study, we show that the number of neurons co-expressing Ctip2 and Satb2, respectively involved in the early specification of subcerebral and callosal projection neurons, progressively increases after birth in the somatosensory cortex. Ctip2/Satb2 postnatal co-localization defines two distinct neuronal subclasses projecting either to the contralateral cortex or to the brainstem suggesting that Ctip2/Satb2 co-expression may refine their properties rather than determine their identity. Gain-and loss-of-function approaches reveal that the transcriptional adaptor Lmo4 drives this maturation program through modulation of epigenetic mechanisms in a time-and area-specific manner, thereby indicating that a previously unknown genetic program postnatally promotes the acquisition of final subtype-specific features. © Harb et al.

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