The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 2002
Two major signaling pathways that control neuronal positioning during brain development have been... more Two major signaling pathways that control neuronal positioning during brain development have been uncovered as a result of genetic and biochemical studies on neurological mouse mutants. Mice deficient in Reelin, Disabled 1 (Dab1), or both the very low-density lipoprotein receptor (VLDLR) and the apolipoprotein E receptor 2 (ApoER2) exhibit identical neuroanatomic defects in laminar structures throughout the brain. These proteins function as components of the Reelin signaling pathway. Reelin is a secreted glycoprotein that binds to VLDLR and ApoER2, inducing tyrosine phosphorylation of Dab1, an intracellular adapter protein. Neuronal migration is also regulated by cyclin-dependent kinase 5 (Cdk5) and its activating subunits p35 and p39. Mice deficient in Cdk5, p35, or both p35 and p39 exhibit lamination defects that are similar but not identical to those observed in mice with a defect in the Reelin signaling pathway. Cdk5 phosphorylates proteins that maintain cytoskeletal structures ...
Reelin, an extracellular matrix molecule, regulates neuronal positioning in the brain, brainstem,... more Reelin, an extracellular matrix molecule, regulates neuronal positioning in the brain, brainstem, and spinal cord. Although Reelin was identified more than a decade ago, its function on neuronal migration is still poorly understood. Using a transgenic mouse that expressed reelin under the nestin promoter, we examined here the function of Reelin in control of sympathetic preganglionic neurons (SPN) migration in the spinal cord. SPN undergo primary and secondary migration to arrive at their final locations. In wildtype mice, postmitotic SPN undergo primary migration from the neuroepithelium to the ventrolateral spinal cord, and then undergo a secondary dorsal migration to their final location to form the intermediolateral column (IML). In reeler, which lacks Reelin, SPN also undergo primary migration to the ventrolateral spinal cord as in wildtype. However, during secondary migration, SPN migrate medially to cluster adjacent to the central canal. Our present study on transgenic rl/rl mutants (rl/rl ne-reelin) shows that the initial migration of SPN (embryonic day [E]9.5-E12.5) was similar to reeler. SPN migrated from the neuroepithelium to the ventrolateral spinal cord and then back toward the central canal, despite strong reelin expression in the ventricular zone. However, SPN did not aggregate near the central canal when ectopic reelin was expressed. Only when the expression level of ectopic reelin in the ventricular zone became very weak (E18.5) were SPN found to cluster near the central canal. Postnatally, SPN in rl/rl ne-reelin transgenic mice were located in both the IML and near the central canal. These results show that SPN position can change with location and level of reelin expression. Possible functions of Reelin on SPN migration are discussed.
This report demonstrates that Clara cell 10-kDa protein (CC10) mRNA levels are regulated by inter... more This report demonstrates that Clara cell 10-kDa protein (CC10) mRNA levels are regulated by interferon-gamma (IFN-gamma). An analysis of total lung RNA from mice given IFN-gamma intratracheally showed increased levels of CC10 mRNA compared to control animals but no significant increases in surfactant proteins B and C. These results were confirmed in a Clara cell line, mtCC1-2, generated from the lungs of a transgenic mouse expressing the SV40 large T antigen under the control of a Clara cell-specific promoter. Significant increases in mtCC1-2 CC10 mRNA levels were observed in a time- and a dose-dependent manner. The expression of transacting factors hepatocyte nuclear factors 3 alpha and 3 beta (HNF-3 alpha and HNF-3 beta) were also analyzed, and a transient increase in the expression of HNF-3 beta but not HNF-3 alpha was detected. Deoxyribonuclease I footprint analysis identified a signal transducer and activator of transcription (STAT) binding site (at nucleotides -293 to -284 of ...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 2002
Two major signaling pathways that control neuronal positioning during brain development have been... more Two major signaling pathways that control neuronal positioning during brain development have been uncovered as a result of genetic and biochemical studies on neurological mouse mutants. Mice deficient in Reelin, Disabled 1 (Dab1), or both the very low-density lipoprotein receptor (VLDLR) and the apolipoprotein E receptor 2 (ApoER2) exhibit identical neuroanatomic defects in laminar structures throughout the brain. These proteins function as components of the Reelin signaling pathway. Reelin is a secreted glycoprotein that binds to VLDLR and ApoER2, inducing tyrosine phosphorylation of Dab1, an intracellular adapter protein. Neuronal migration is also regulated by cyclin-dependent kinase 5 (Cdk5) and its activating subunits p35 and p39. Mice deficient in Cdk5, p35, or both p35 and p39 exhibit lamination defects that are similar but not identical to those observed in mice with a defect in the Reelin signaling pathway. Cdk5 phosphorylates proteins that maintain cytoskeletal structures ...
Reelin, an extracellular matrix molecule, regulates neuronal positioning in the brain, brainstem,... more Reelin, an extracellular matrix molecule, regulates neuronal positioning in the brain, brainstem, and spinal cord. Although Reelin was identified more than a decade ago, its function on neuronal migration is still poorly understood. Using a transgenic mouse that expressed reelin under the nestin promoter, we examined here the function of Reelin in control of sympathetic preganglionic neurons (SPN) migration in the spinal cord. SPN undergo primary and secondary migration to arrive at their final locations. In wildtype mice, postmitotic SPN undergo primary migration from the neuroepithelium to the ventrolateral spinal cord, and then undergo a secondary dorsal migration to their final location to form the intermediolateral column (IML). In reeler, which lacks Reelin, SPN also undergo primary migration to the ventrolateral spinal cord as in wildtype. However, during secondary migration, SPN migrate medially to cluster adjacent to the central canal. Our present study on transgenic rl/rl mutants (rl/rl ne-reelin) shows that the initial migration of SPN (embryonic day [E]9.5-E12.5) was similar to reeler. SPN migrated from the neuroepithelium to the ventrolateral spinal cord and then back toward the central canal, despite strong reelin expression in the ventricular zone. However, SPN did not aggregate near the central canal when ectopic reelin was expressed. Only when the expression level of ectopic reelin in the ventricular zone became very weak (E18.5) were SPN found to cluster near the central canal. Postnatally, SPN in rl/rl ne-reelin transgenic mice were located in both the IML and near the central canal. These results show that SPN position can change with location and level of reelin expression. Possible functions of Reelin on SPN migration are discussed.
This report demonstrates that Clara cell 10-kDa protein (CC10) mRNA levels are regulated by inter... more This report demonstrates that Clara cell 10-kDa protein (CC10) mRNA levels are regulated by interferon-gamma (IFN-gamma). An analysis of total lung RNA from mice given IFN-gamma intratracheally showed increased levels of CC10 mRNA compared to control animals but no significant increases in surfactant proteins B and C. These results were confirmed in a Clara cell line, mtCC1-2, generated from the lungs of a transgenic mouse expressing the SV40 large T antigen under the control of a Clara cell-specific promoter. Significant increases in mtCC1-2 CC10 mRNA levels were observed in a time- and a dose-dependent manner. The expression of transacting factors hepatocyte nuclear factors 3 alpha and 3 beta (HNF-3 alpha and HNF-3 beta) were also analyzed, and a transient increase in the expression of HNF-3 beta but not HNF-3 alpha was detected. Deoxyribonuclease I footprint analysis identified a signal transducer and activator of transcription (STAT) binding site (at nucleotides -293 to -284 of ...
Uploads
Papers by Susan Magdaleno