Reprogramming of neonatal SVZ progenitors by islet-1 and neurogenin-2.
The subventricular zone (SVZ) lining the lateral walls of the lateral ventricles is one of the major neurogenic areas in the postnatal brain. Precursor cells in the SVZ migrate via the rostral migratory stream to the olfactory bulb where they differentiate into neurons. Cell replacement strategies utilizing the recruitment of these endogenous progenitors and their progeny to different areas of the brain hold great promise for the future, but much research is needed in order to understand the sequence of molecular signals necessary to induce proliferation, migration and site-specific differentiation of these cells. In this study we show that the SVZ cells can be redirected from their normal migration route and directed towards other brain regions when they are infected with retroviruses encoding the developmentally important transcription factors Islet-1 and Neurogenin-2. After co-transduction with these transcription factors, transduced cells could be detected in several areas of the brain. When located in the striatum, the reprogrammed cells displayed neuroblast-like morphology. Once removed from the striatal parenchyma and allowed to further differentiation in vitro they developed into beta-III-tubulin positive neurons.
Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, BMC A11, SE-221 84 Lund, Sweden. Malin.Parmar@med.lu.se
Nina
N
Rogelius
Josephine B
JB
Hebsgaard
Cecilia
C
Lundberg
Malin
M
Parmar
D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics* / Q000502:physiology; D002478:Cells, Cultured; D002552:Cerebral Ventricles / Q000166:cytology* / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D005822:Genetic Vectors; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D060850:LIM-Homeodomain Proteins; D020547:Lateral Ventricles / Q000166:cytology / Q000502:physiology / Q000821:virology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012190:Retroviridae / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D014157:Transcription Factors; D014161:Transduction, Genetic
D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C491183:NEUROG2 protein, human; C063843:insulin gene enhancer binding protein Isl-1