Identification of two distinct progenitor populations in the lateral ganglionic eminence: implications for striatal and olfactory bulb neurogenesis.
The lateral ganglionic eminence (LGE) is known to give rise to striatal projection neurons as well as interneurons, which migrate in the rostral migratory stream (RMS) to populate the granule cell and glomerular layers of the olfactory bulb. Because all of these neuronal subtypes express Distalless-related (DLX) homeobox proteins during their differentiation, we set out to further characterize progenitors in the Dlx-positive domain of the LGE. Previous studies have shown that the LIM homeobox protein Islet1 (ISL1) marks the LGE subventricular zone (SVZ) and differentiating striatal projection neurons. However, ISL1 is not expressed in neurons of the developing olfactory bulb or the RMS. We show here that the dorsal-most portion of the Dlx-expressing region of the LGE SVZ lacks ISL1 cells. This dorsal domain, however, contains cells that express the ETS transcription factor Er81, which is also expressed in granule and periglomerular cells of the developing and adult olfactory bulb. Moreover, the adult SVZ and RMS contain numerous Er81-positive cells. Fate-mapping studies using Dlx5/6-cre transgenic mice demonstrate that Er81-positive cells in the granule cell and glomerular layers of the olfactory bulb derive from the Dlx-expressing SVZ region. These findings suggest that the LGE SVZ contains two distinct progenitor populations: a DLX(+);ISL1(+) population representing striatal progenitors and a DLX(+);Er81(+) population comprising olfactory bulb interneuron progenitors. In support of this, mice mutant for the homeobox genes Gsh2 and Gsh1/2, which show olfactory bulb defects, exhibit dramatically reduced numbers of Er81-positive cells in the LGE SVZ as well as in the olfactory bulb mantle.
Stenman
Jan
J
Division of Developmental Biology, Children's Hospital Research Foundation, Cincinnati, Ohio 45229-3039, USA.
Toresson
Hakan
H
Campbell
Kenneth
K
D000818:Animals; D003342:Corpus Striatum / Q000166:cytology / Q000196:embryology*; D004268:DNA-Binding Proteins / Q000032:analysis; D005724:Ganglia / Q000166:cytology; D049452:Green Fluorescent Proteins; D018398:Homeodomain Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D019426:Integrases / Q000235:genetics; D007395:Interneurons / Q000737:chemistry / Q000166:cytology; D060850:LIM-Homeodomain Proteins; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000737:chemistry / Q000166:cytology; D009830:Olfactory Bulb / Q000166:cytology / Q000196:embryology* / Q000254:growth & development; D013234:Stem Cells / Q000737:chemistry* / Q000378:metabolism; D013687:Telencephalon / Q000737:chemistry / Q000166:cytology* / Q000196:embryology*; D014157:Transcription Factors / Q000032:analysis; D014764:Viral Proteins / Q000235:genetics
C491014:DLX6 protein, human; D004268:DNA-Binding Proteins; C501120:Dlx5 protein, mouse; C100597:Dlx6 protein, mouse; C490641:Etv1 protein, mouse; C098513:Gsh1 protein, mouse; C109498:Gsh2 protein, mouse; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D014764:Viral Proteins; C063843:insulin gene enhancer binding protein Isl-1; D049452:Green Fluorescent Proteins; C045073:Cre recombinase; D019426:Integrases