Neural stem cells (NSCs) generate distinct cell types for tissue formation and cell replacement during development and throughout adulthood. At the molecular level, neural development and plasticity are determined by both extrinsic and intrinsic factors that crosstalk to regulate the genetic programs governing NSC fate specification. Previous work from our and other labs has shown that NSCs derived from different regions of the mouse foetal central nervous system (CNS) maintain in vitro expression profiles of markers of regional identity that are consistent with their region of derivation in vivo. For example, NSCs derived from the embryonic cortex and striatum express the forebrain markers FoxG1 and Otx2, but not the hindbrain/spinal cord markers HoxB4/6/9, while the opposite pattern is detectable in NSCs from the embryonic spinal cord. However, it is currently unclear whether these regional identities are irreversibly specified and can be maintained in vitro even after exposure to molecular cues involved in CNS patterning. To this aim, cortex-, striatum- and spinal cord-derived NSCs were treated with different concentrations of morphogens that have a well-established role in specifying posterior cell fates and promoting Hox gene expression in the developing CNS, namely Retinoic Acid (RA) and Fibroblast Growth Factor (FGF). We found that only spinal cord-derived NSCs were able to respond to RA and FGF by further upregulating HoxB4/6/9 expression compared to control levels. By contrast, cortex- and striatum-derived NSCs maintained forebrain-specific gene expression patterns and did not upregulate HoxB genes regardless of RA and FGF treatments. These results suggest that the developmental plasticity of NPCs is restricted at an early phase of neural development through mechanisms that can be maintained in vitro even after exposure to exogenous morphogens. Further experiments are underway in order to elucidate the molecular mechanisms that control the differential response of region-specific NSCs to RA and FGF.
Maintenance of positional identities in region-specific neural stem cell lines following exposure to exogenous morphogens in vitro / N., Carucci; Cacci, Emanuele; G., Augusti Tocco; Biagioni, Stefano; G., Lupo. - (2011). (Intervento presentato al convegno Molecular Mechanisms in Neurosciences tenutosi a Rome nel 3-4 ottobre 2011).
Maintenance of positional identities in region-specific neural stem cell lines following exposure to exogenous morphogens in vitro.
CACCI, Emanuele;BIAGIONI, Stefano;
2011
Abstract
Neural stem cells (NSCs) generate distinct cell types for tissue formation and cell replacement during development and throughout adulthood. At the molecular level, neural development and plasticity are determined by both extrinsic and intrinsic factors that crosstalk to regulate the genetic programs governing NSC fate specification. Previous work from our and other labs has shown that NSCs derived from different regions of the mouse foetal central nervous system (CNS) maintain in vitro expression profiles of markers of regional identity that are consistent with their region of derivation in vivo. For example, NSCs derived from the embryonic cortex and striatum express the forebrain markers FoxG1 and Otx2, but not the hindbrain/spinal cord markers HoxB4/6/9, while the opposite pattern is detectable in NSCs from the embryonic spinal cord. However, it is currently unclear whether these regional identities are irreversibly specified and can be maintained in vitro even after exposure to molecular cues involved in CNS patterning. To this aim, cortex-, striatum- and spinal cord-derived NSCs were treated with different concentrations of morphogens that have a well-established role in specifying posterior cell fates and promoting Hox gene expression in the developing CNS, namely Retinoic Acid (RA) and Fibroblast Growth Factor (FGF). We found that only spinal cord-derived NSCs were able to respond to RA and FGF by further upregulating HoxB4/6/9 expression compared to control levels. By contrast, cortex- and striatum-derived NSCs maintained forebrain-specific gene expression patterns and did not upregulate HoxB genes regardless of RA and FGF treatments. These results suggest that the developmental plasticity of NPCs is restricted at an early phase of neural development through mechanisms that can be maintained in vitro even after exposure to exogenous morphogens. Further experiments are underway in order to elucidate the molecular mechanisms that control the differential response of region-specific NSCs to RA and FGF.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.