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- Stenman, Jan, et al.
(författare)
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Identification of two distinct progenitor populations in the lateral ganglionic eminence: Implications for striatal and olfactory bulb neurogenesis
- 2003
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Ingår i: The Journal of Neuroscience. - 1529-2401. ; 23:1, s. 167-174
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Toresson, Håkan, et al.
(författare)
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Expression of Meis and Pbx genes and their protein products in the developing telencephalon : Implications for regional differentiation
- 2000
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Ingår i: Mechanisms of Development. - 0925-4773. ; 94:1-2, s. 183-187
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Tidskriftsartikel (refereegranskat)abstract
- The Meis and Pbx genes encode for homeodomain proteins of the TALE class and have been shown to act as co-factors for other homeodomain transcription factors (Mann and Affolter, 1998. Curr. Opin. Genet. Dev. 8, 423-429). We have studied the expression of these genes in the mouse telencephalon and found that Meis1 and Meis2 display region-specific patterns of expression from embryonic day (E)10.5 until birth, defining distinct subterritories in the developing telencephalon. The expression of the Meis genes and their proteins is highest in the subventricular zone (SVZ) and mantle regions of the ventral telencephalon. Compared to the Meis genes, Pbx genes show a broader expression within the telencephalon. However, as is the case in Drosophila (Rieckhof et al., 1997. Cell 91, 171-183; Kurrant et al., 1998. Development 125, 1037-1048; Pai et al., 1998. Genes Dev. 12, 435-446), nuclear localized PBX proteins were found to correlate highly with Meis expression. In addition, DLX proteins co-localize with nuclear PBX in distinct regions of the ventral telencephalon. (C) 2000 Elsevier Science Ireland Ltd. (C) 2000 Elsevier Science Ireland Ltd.
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| 3. |
- Toresson, Håkan
(författare)
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Mechanisms controlling striatal projection neurone generation, from patterning to early differentiation
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The striatum is part of the telencephalon, the most anterior part of the vertebrate brain. From when it first can be identified, telencephalic morphology is highly complex and a wide range of mechanisms has been suggested to participate in its induction, patterning and neurogenesis. Sonic hedgehog (shh), a gene coding for a secreted protein has been suggested to be required for ventral telencephalic, including striatal, development. The first study in this thesis demonstrates that shh is important for striatal development but that aspects of this process can occur in shh mutant mice. Once the lateral ganglionic eminence (LGE, the source of striatal projection neurones) has been defined, mechanisms are required to ensure correct identity of striatal progenitor cells. The second study shows that two homeodomain transcription factor genes control aspects of this: Pax6, which is expressed in cortical progenitors and Gsh2 found in striatal progenitors. By analysing mice, mutant for either one or both of these genes, we concluded that they oppositely regulate the identity of cortical and striatal progenitors. Interestingly, we were able to demonstrate that in the absence of Gsh2, the highly similar gene Gsh1 rescues aspects of striatal development (paper III) while other aspects appear Gsh gene-independent.. When striatal neurogenesis has started, post-mitotic cells most likely rely on cell-intrinsic as well as cell-extrinsic mechanisms to ensure correct differentiation. In study four we describe the identification of candidates to the first category; homeodomain genes of the Meis and Pbx family. Finally, in the fifth study, retinoids are presented as a candidate cell-extrinsic regulator of striatal projection neurone development.
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