Retrovirally delivered Islet-1 increases recruitment of Ng2 expressing cells from the postnatal SVZ into the striatum.
Neural stem and progenitor cells hold the promise to be used in cell-based therapies to treat both acute and degenerative neurological diseases. To date, most research has been focused on the use of in vitro propagated stem cells used as a source of cells in cell replacement therapies. However, mobilization of endogenous neural stem cells to generate a specific differentiated cell type offers an attractive alternative. In this study, we investigate the possibility to direct the formation of specific cells from the endogenous stem and progenitor cells residing in the subventricular region of the postnatal brain. With the aim to induce postnatal generation of striatal neurons, we ectopically expressed Islet-1, a LIM homeodomain transcription factor expressed by striatal progenitors during development, in cells of the subventricular zone (SVZ) of neonatal and adult rats. Ectopic expression of Islet-1 in the neonatal, but not adult, SVZ resulted in the appearance of a population of cells in the striatum. These cells were primarily located in the ventrolateral area of the striatum where they differentiate into Ng2 expressing cells. However, no neurogenesis was observed in the striatum, nor was ectopic striatal differentiation observed in any other area of the brain after retroviral expression of Islet-1 in the SVZ. Thus, although ectopic expression of Islet-1 is sufficient to direct the migration of cells into the striatum in neonatal animals, it does not specify a striatal projection neuron phenotype in cells generated from the SVZ after birth.
Rogelius
Nina
N
Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, BMC A11, Lund, Sweden. Nina.Rogelius@med.lu.se
Jensen
Josephine B
JB
Lundberg
Cecilia
C
Parmar
Malin
M
D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000378:metabolism*; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism*; D005822:Genetic Vectors / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology; D007150:Immunohistochemistry; D060850:LIM-Homeodomain Proteins; D051379:Mice; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors; D014162:Transfection / Q000379:methods; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D005904:Glial Fibrillary Acidic Protein; D049452:Green Fluorescent Proteins; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D011509:Proteoglycans; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D000099216:Chondroitin Sulfate Proteoglycan 4; C063843:insulin gene enhancer binding protein Isl-1