A forward genetic screen with a thalamocortical axon reporter mouse yields novel neurodevelopment mutants and a distinct <it<emx2 </it<mutant phenotype

<p<Abstract</p< <p<Background</p< <p<The dorsal thalamus acts as a gateway and modulator for information going to and from the cerebral cortex. This activity requires the formation of reciprocal topographic axon connections between thalamus and cortex. The axons grow along a complex multistep pathway, making sharp turns, crossing expression boundaries, and encountering intermediate targets. However, the cellular and molecular components mediating these steps remain poorly understood.</p< <p<Results</p< <p<To further elucidate the development of the thalamocortical system, we first created a thalamocortical axon reporter line to use as a genetic tool for sensitive analysis of mutant mouse phenotypes. The TCA-<it<tau-lacZ </it<reporter mouse shows specific, robust, and reproducible labeling of thalamocortical axons (TCAs), but not the overlapping corticothalamic axons, during development. Moreover, it readily reveals TCA pathfinding abnormalities in known cortical mutants such as <it<reeler</it<. Next, we performed an unbiased screen for genes involved in thalamocortical development using random mutagenesis with the TCA reporter. Six independent mutant lines show aberrant TCA phenotypes at different steps of the pathway. These include ventral misrouting, overfasciculation, stalling at the corticostriatal boundary, and invasion of ectopic cortical cell clusters. An outcross breeding strategy coupled with a genomic panel of single nucleotide polymorphisms facilitated genetic mapping with small numbers of mutant mice. We mapped a ventral misrouting mutant to the <it<Emx2 </it<gene, and discovered that some TCAs extend to the olfactory bulbs in this mutant. Mapping data suggest that other lines carry mutations in genes not previously known for roles in thalamocortical development.</p< <p<Conclusions</p< <p<These data demonstrate the feasibility of a forward genetic approach to understanding mammalian brain morphogenesis and wiring. A robust axonal reporter enabled sensitive analysis of a specific axon tract inside the mouse brain, identifying mutant phenotypes at multiple steps of the pathway, and revealing a new aspect of the <it<Emx2 </it<mutant. The phenotypes highlight vulnerable choice points and latent tendencies of TCAs, and will lead to a refined understanding of the elements and interactions required to form the thalamocortical system.</p< <p<See Commentary: <url<http://www.biomedcentral.com/1741-7007/9/1</url<</p< Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Vock Vita M [verfasserIn] Favero Carlita B [verfasserIn] Fleming Michael S [verfasserIn] Mudbhary Raksha [verfasserIn] Moran Jennifer L [verfasserIn] Manning Danielle K [verfasserIn] Dwyer Noelle D [verfasserIn] O'Leary Dennis DM [verfasserIn] Walsh Christopher A [verfasserIn] Beier David R [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2011

Übergeordnetes Werk:	In: Neural Development - BMC, 2006, 6(2011), 1, p 3
Übergeordnetes Werk:	volume:6 ; year:2011 ; number:1, p 3

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/1749-8104-6-3

Katalog-ID:	DOAJ05948571X

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allfields	10.1186/1749-8104-6-3 doi (DE-627)DOAJ05948571X (DE-599)DOAJ65c18e74d221495f843f318aeee548e1 DE-627 ger DE-627 rakwb eng RC346-429 Vock Vita M verfasserin aut A forward genetic screen with a thalamocortical axon reporter mouse yields novel neurodevelopment mutants and a distinct <it<emx2 </it<mutant phenotype 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<The dorsal thalamus acts as a gateway and modulator for information going to and from the cerebral cortex. This activity requires the formation of reciprocal topographic axon connections between thalamus and cortex. The axons grow along a complex multistep pathway, making sharp turns, crossing expression boundaries, and encountering intermediate targets. However, the cellular and molecular components mediating these steps remain poorly understood.</p< <p<Results</p< <p<To further elucidate the development of the thalamocortical system, we first created a thalamocortical axon reporter line to use as a genetic tool for sensitive analysis of mutant mouse phenotypes. The TCA-<it<tau-lacZ </it<reporter mouse shows specific, robust, and reproducible labeling of thalamocortical axons (TCAs), but not the overlapping corticothalamic axons, during development. Moreover, it readily reveals TCA pathfinding abnormalities in known cortical mutants such as <it<reeler</it<. Next, we performed an unbiased screen for genes involved in thalamocortical development using random mutagenesis with the TCA reporter. Six independent mutant lines show aberrant TCA phenotypes at different steps of the pathway. These include ventral misrouting, overfasciculation, stalling at the corticostriatal boundary, and invasion of ectopic cortical cell clusters. An outcross breeding strategy coupled with a genomic panel of single nucleotide polymorphisms facilitated genetic mapping with small numbers of mutant mice. We mapped a ventral misrouting mutant to the <it<Emx2 </it<gene, and discovered that some TCAs extend to the olfactory bulbs in this mutant. Mapping data suggest that other lines carry mutations in genes not previously known for roles in thalamocortical development.</p< <p<Conclusions</p< <p<These data demonstrate the feasibility of a forward genetic approach to understanding mammalian brain morphogenesis and wiring. A robust axonal reporter enabled sensitive analysis of a specific axon tract inside the mouse brain, identifying mutant phenotypes at multiple steps of the pathway, and revealing a new aspect of the <it<Emx2 </it<mutant. The phenotypes highlight vulnerable choice points and latent tendencies of TCAs, and will lead to a refined understanding of the elements and interactions required to form the thalamocortical system.</p< <p<See Commentary: <url<http://www.biomedcentral.com/1741-7007/9/1</url<</p< Neurology. Diseases of the nervous system Favero Carlita B verfasserin aut Fleming Michael S verfasserin aut Mudbhary Raksha verfasserin aut Moran Jennifer L verfasserin aut Manning Danielle K verfasserin aut Dwyer Noelle D verfasserin aut O'Leary Dennis DM verfasserin aut Walsh Christopher A verfasserin aut Beier David R verfasserin aut In Neural Development BMC, 2006 6(2011), 1, p 3 (DE-627)519199669 (DE-600)2254847-6 17498104 nnns volume:6 year:2011 number:1, p 3 https://doi.org/10.1186/1749-8104-6-3 kostenfrei https://doaj.org/article/65c18e74d221495f843f318aeee548e1 kostenfrei http://www.neuraldevelopment.com/content/6/1/3 kostenfrei https://doaj.org/toc/1749-8104 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2011 1, p 3
spelling	10.1186/1749-8104-6-3 doi (DE-627)DOAJ05948571X (DE-599)DOAJ65c18e74d221495f843f318aeee548e1 DE-627 ger DE-627 rakwb eng RC346-429 Vock Vita M verfasserin aut A forward genetic screen with a thalamocortical axon reporter mouse yields novel neurodevelopment mutants and a distinct <it<emx2 </it<mutant phenotype 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<The dorsal thalamus acts as a gateway and modulator for information going to and from the cerebral cortex. This activity requires the formation of reciprocal topographic axon connections between thalamus and cortex. The axons grow along a complex multistep pathway, making sharp turns, crossing expression boundaries, and encountering intermediate targets. However, the cellular and molecular components mediating these steps remain poorly understood.</p< <p<Results</p< <p<To further elucidate the development of the thalamocortical system, we first created a thalamocortical axon reporter line to use as a genetic tool for sensitive analysis of mutant mouse phenotypes. The TCA-<it<tau-lacZ </it<reporter mouse shows specific, robust, and reproducible labeling of thalamocortical axons (TCAs), but not the overlapping corticothalamic axons, during development. Moreover, it readily reveals TCA pathfinding abnormalities in known cortical mutants such as <it<reeler</it<. Next, we performed an unbiased screen for genes involved in thalamocortical development using random mutagenesis with the TCA reporter. Six independent mutant lines show aberrant TCA phenotypes at different steps of the pathway. These include ventral misrouting, overfasciculation, stalling at the corticostriatal boundary, and invasion of ectopic cortical cell clusters. An outcross breeding strategy coupled with a genomic panel of single nucleotide polymorphisms facilitated genetic mapping with small numbers of mutant mice. We mapped a ventral misrouting mutant to the <it<Emx2 </it<gene, and discovered that some TCAs extend to the olfactory bulbs in this mutant. Mapping data suggest that other lines carry mutations in genes not previously known for roles in thalamocortical development.</p< <p<Conclusions</p< <p<These data demonstrate the feasibility of a forward genetic approach to understanding mammalian brain morphogenesis and wiring. A robust axonal reporter enabled sensitive analysis of a specific axon tract inside the mouse brain, identifying mutant phenotypes at multiple steps of the pathway, and revealing a new aspect of the <it<Emx2 </it<mutant. The phenotypes highlight vulnerable choice points and latent tendencies of TCAs, and will lead to a refined understanding of the elements and interactions required to form the thalamocortical system.</p< <p<See Commentary: <url<http://www.biomedcentral.com/1741-7007/9/1</url<</p< Neurology. Diseases of the nervous system Favero Carlita B verfasserin aut Fleming Michael S verfasserin aut Mudbhary Raksha verfasserin aut Moran Jennifer L verfasserin aut Manning Danielle K verfasserin aut Dwyer Noelle D verfasserin aut O'Leary Dennis DM verfasserin aut Walsh Christopher A verfasserin aut Beier David R verfasserin aut In Neural Development BMC, 2006 6(2011), 1, p 3 (DE-627)519199669 (DE-600)2254847-6 17498104 nnns volume:6 year:2011 number:1, p 3 https://doi.org/10.1186/1749-8104-6-3 kostenfrei https://doaj.org/article/65c18e74d221495f843f318aeee548e1 kostenfrei http://www.neuraldevelopment.com/content/6/1/3 kostenfrei https://doaj.org/toc/1749-8104 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2011 1, p 3
allfields_unstemmed	10.1186/1749-8104-6-3 doi (DE-627)DOAJ05948571X (DE-599)DOAJ65c18e74d221495f843f318aeee548e1 DE-627 ger DE-627 rakwb eng RC346-429 Vock Vita M verfasserin aut A forward genetic screen with a thalamocortical axon reporter mouse yields novel neurodevelopment mutants and a distinct <it<emx2 </it<mutant phenotype 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<The dorsal thalamus acts as a gateway and modulator for information going to and from the cerebral cortex. This activity requires the formation of reciprocal topographic axon connections between thalamus and cortex. The axons grow along a complex multistep pathway, making sharp turns, crossing expression boundaries, and encountering intermediate targets. However, the cellular and molecular components mediating these steps remain poorly understood.</p< <p<Results</p< <p<To further elucidate the development of the thalamocortical system, we first created a thalamocortical axon reporter line to use as a genetic tool for sensitive analysis of mutant mouse phenotypes. The TCA-<it<tau-lacZ </it<reporter mouse shows specific, robust, and reproducible labeling of thalamocortical axons (TCAs), but not the overlapping corticothalamic axons, during development. Moreover, it readily reveals TCA pathfinding abnormalities in known cortical mutants such as <it<reeler</it<. Next, we performed an unbiased screen for genes involved in thalamocortical development using random mutagenesis with the TCA reporter. Six independent mutant lines show aberrant TCA phenotypes at different steps of the pathway. These include ventral misrouting, overfasciculation, stalling at the corticostriatal boundary, and invasion of ectopic cortical cell clusters. An outcross breeding strategy coupled with a genomic panel of single nucleotide polymorphisms facilitated genetic mapping with small numbers of mutant mice. We mapped a ventral misrouting mutant to the <it<Emx2 </it<gene, and discovered that some TCAs extend to the olfactory bulbs in this mutant. Mapping data suggest that other lines carry mutations in genes not previously known for roles in thalamocortical development.</p< <p<Conclusions</p< <p<These data demonstrate the feasibility of a forward genetic approach to understanding mammalian brain morphogenesis and wiring. A robust axonal reporter enabled sensitive analysis of a specific axon tract inside the mouse brain, identifying mutant phenotypes at multiple steps of the pathway, and revealing a new aspect of the <it<Emx2 </it<mutant. The phenotypes highlight vulnerable choice points and latent tendencies of TCAs, and will lead to a refined understanding of the elements and interactions required to form the thalamocortical system.</p< <p<See Commentary: <url<http://www.biomedcentral.com/1741-7007/9/1</url<</p< Neurology. Diseases of the nervous system Favero Carlita B verfasserin aut Fleming Michael S verfasserin aut Mudbhary Raksha verfasserin aut Moran Jennifer L verfasserin aut Manning Danielle K verfasserin aut Dwyer Noelle D verfasserin aut O'Leary Dennis DM verfasserin aut Walsh Christopher A verfasserin aut Beier David R verfasserin aut In Neural Development BMC, 2006 6(2011), 1, p 3 (DE-627)519199669 (DE-600)2254847-6 17498104 nnns volume:6 year:2011 number:1, p 3 https://doi.org/10.1186/1749-8104-6-3 kostenfrei https://doaj.org/article/65c18e74d221495f843f318aeee548e1 kostenfrei http://www.neuraldevelopment.com/content/6/1/3 kostenfrei https://doaj.org/toc/1749-8104 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2011 1, p 3
allfieldsGer	10.1186/1749-8104-6-3 doi (DE-627)DOAJ05948571X (DE-599)DOAJ65c18e74d221495f843f318aeee548e1 DE-627 ger DE-627 rakwb eng RC346-429 Vock Vita M verfasserin aut A forward genetic screen with a thalamocortical axon reporter mouse yields novel neurodevelopment mutants and a distinct <it<emx2 </it<mutant phenotype 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<The dorsal thalamus acts as a gateway and modulator for information going to and from the cerebral cortex. This activity requires the formation of reciprocal topographic axon connections between thalamus and cortex. The axons grow along a complex multistep pathway, making sharp turns, crossing expression boundaries, and encountering intermediate targets. However, the cellular and molecular components mediating these steps remain poorly understood.</p< <p<Results</p< <p<To further elucidate the development of the thalamocortical system, we first created a thalamocortical axon reporter line to use as a genetic tool for sensitive analysis of mutant mouse phenotypes. The TCA-<it<tau-lacZ </it<reporter mouse shows specific, robust, and reproducible labeling of thalamocortical axons (TCAs), but not the overlapping corticothalamic axons, during development. Moreover, it readily reveals TCA pathfinding abnormalities in known cortical mutants such as <it<reeler</it<. Next, we performed an unbiased screen for genes involved in thalamocortical development using random mutagenesis with the TCA reporter. Six independent mutant lines show aberrant TCA phenotypes at different steps of the pathway. These include ventral misrouting, overfasciculation, stalling at the corticostriatal boundary, and invasion of ectopic cortical cell clusters. An outcross breeding strategy coupled with a genomic panel of single nucleotide polymorphisms facilitated genetic mapping with small numbers of mutant mice. We mapped a ventral misrouting mutant to the <it<Emx2 </it<gene, and discovered that some TCAs extend to the olfactory bulbs in this mutant. Mapping data suggest that other lines carry mutations in genes not previously known for roles in thalamocortical development.</p< <p<Conclusions</p< <p<These data demonstrate the feasibility of a forward genetic approach to understanding mammalian brain morphogenesis and wiring. A robust axonal reporter enabled sensitive analysis of a specific axon tract inside the mouse brain, identifying mutant phenotypes at multiple steps of the pathway, and revealing a new aspect of the <it<Emx2 </it<mutant. The phenotypes highlight vulnerable choice points and latent tendencies of TCAs, and will lead to a refined understanding of the elements and interactions required to form the thalamocortical system.</p< <p<See Commentary: <url<http://www.biomedcentral.com/1741-7007/9/1</url<</p< Neurology. Diseases of the nervous system Favero Carlita B verfasserin aut Fleming Michael S verfasserin aut Mudbhary Raksha verfasserin aut Moran Jennifer L verfasserin aut Manning Danielle K verfasserin aut Dwyer Noelle D verfasserin aut O'Leary Dennis DM verfasserin aut Walsh Christopher A verfasserin aut Beier David R verfasserin aut In Neural Development BMC, 2006 6(2011), 1, p 3 (DE-627)519199669 (DE-600)2254847-6 17498104 nnns volume:6 year:2011 number:1, p 3 https://doi.org/10.1186/1749-8104-6-3 kostenfrei https://doaj.org/article/65c18e74d221495f843f318aeee548e1 kostenfrei http://www.neuraldevelopment.com/content/6/1/3 kostenfrei https://doaj.org/toc/1749-8104 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2011 1, p 3
allfieldsSound	10.1186/1749-8104-6-3 doi (DE-627)DOAJ05948571X (DE-599)DOAJ65c18e74d221495f843f318aeee548e1 DE-627 ger DE-627 rakwb eng RC346-429 Vock Vita M verfasserin aut A forward genetic screen with a thalamocortical axon reporter mouse yields novel neurodevelopment mutants and a distinct <it<emx2 </it<mutant phenotype 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<The dorsal thalamus acts as a gateway and modulator for information going to and from the cerebral cortex. This activity requires the formation of reciprocal topographic axon connections between thalamus and cortex. The axons grow along a complex multistep pathway, making sharp turns, crossing expression boundaries, and encountering intermediate targets. However, the cellular and molecular components mediating these steps remain poorly understood.</p< <p<Results</p< <p<To further elucidate the development of the thalamocortical system, we first created a thalamocortical axon reporter line to use as a genetic tool for sensitive analysis of mutant mouse phenotypes. The TCA-<it<tau-lacZ </it<reporter mouse shows specific, robust, and reproducible labeling of thalamocortical axons (TCAs), but not the overlapping corticothalamic axons, during development. Moreover, it readily reveals TCA pathfinding abnormalities in known cortical mutants such as <it<reeler</it<. Next, we performed an unbiased screen for genes involved in thalamocortical development using random mutagenesis with the TCA reporter. Six independent mutant lines show aberrant TCA phenotypes at different steps of the pathway. These include ventral misrouting, overfasciculation, stalling at the corticostriatal boundary, and invasion of ectopic cortical cell clusters. An outcross breeding strategy coupled with a genomic panel of single nucleotide polymorphisms facilitated genetic mapping with small numbers of mutant mice. We mapped a ventral misrouting mutant to the <it<Emx2 </it<gene, and discovered that some TCAs extend to the olfactory bulbs in this mutant. Mapping data suggest that other lines carry mutations in genes not previously known for roles in thalamocortical development.</p< <p<Conclusions</p< <p<These data demonstrate the feasibility of a forward genetic approach to understanding mammalian brain morphogenesis and wiring. A robust axonal reporter enabled sensitive analysis of a specific axon tract inside the mouse brain, identifying mutant phenotypes at multiple steps of the pathway, and revealing a new aspect of the <it<Emx2 </it<mutant. The phenotypes highlight vulnerable choice points and latent tendencies of TCAs, and will lead to a refined understanding of the elements and interactions required to form the thalamocortical system.</p< <p<See Commentary: <url<http://www.biomedcentral.com/1741-7007/9/1</url<</p< Neurology. Diseases of the nervous system Favero Carlita B verfasserin aut Fleming Michael S verfasserin aut Mudbhary Raksha verfasserin aut Moran Jennifer L verfasserin aut Manning Danielle K verfasserin aut Dwyer Noelle D verfasserin aut O'Leary Dennis DM verfasserin aut Walsh Christopher A verfasserin aut Beier David R verfasserin aut In Neural Development BMC, 2006 6(2011), 1, p 3 (DE-627)519199669 (DE-600)2254847-6 17498104 nnns volume:6 year:2011 number:1, p 3 https://doi.org/10.1186/1749-8104-6-3 kostenfrei https://doaj.org/article/65c18e74d221495f843f318aeee548e1 kostenfrei http://www.neuraldevelopment.com/content/6/1/3 kostenfrei https://doaj.org/toc/1749-8104 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2011 1, p 3
language	English
source	In Neural Development 6(2011), 1, p 3 volume:6 year:2011 number:1, p 3
sourceStr	In Neural Development 6(2011), 1, p 3 volume:6 year:2011 number:1, p 3
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Neurology. Diseases of the nervous system
isfreeaccess_bool	true
container_title	Neural Development
authorswithroles_txt_mv	Vock Vita M @@aut@@ Favero Carlita B @@aut@@ Fleming Michael S @@aut@@ Mudbhary Raksha @@aut@@ Moran Jennifer L @@aut@@ Manning Danielle K @@aut@@ Dwyer Noelle D @@aut@@ O'Leary Dennis DM @@aut@@ Walsh Christopher A @@aut@@ Beier David R @@aut@@
publishDateDaySort_date	2011-01-01T00:00:00Z
hierarchy_top_id	519199669
id	DOAJ05948571X
language_de	englisch
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This activity requires the formation of reciprocal topographic axon connections between thalamus and cortex. The axons grow along a complex multistep pathway, making sharp turns, crossing expression boundaries, and encountering intermediate targets. However, the cellular and molecular components mediating these steps remain poorly understood.</p< <p<Results</p< <p<To further elucidate the development of the thalamocortical system, we first created a thalamocortical axon reporter line to use as a genetic tool for sensitive analysis of mutant mouse phenotypes. The TCA-<it<tau-lacZ </it<reporter mouse shows specific, robust, and reproducible labeling of thalamocortical axons (TCAs), but not the overlapping corticothalamic axons, during development. Moreover, it readily reveals TCA pathfinding abnormalities in known cortical mutants such as <it<reeler</it<. Next, we performed an unbiased screen for genes involved in thalamocortical development using random mutagenesis with the TCA reporter. Six independent mutant lines show aberrant TCA phenotypes at different steps of the pathway. These include ventral misrouting, overfasciculation, stalling at the corticostriatal boundary, and invasion of ectopic cortical cell clusters. An outcross breeding strategy coupled with a genomic panel of single nucleotide polymorphisms facilitated genetic mapping with small numbers of mutant mice. We mapped a ventral misrouting mutant to the <it<Emx2 </it<gene, and discovered that some TCAs extend to the olfactory bulbs in this mutant. Mapping data suggest that other lines carry mutations in genes not previously known for roles in thalamocortical development.</p< <p<Conclusions</p< <p<These data demonstrate the feasibility of a forward genetic approach to understanding mammalian brain morphogenesis and wiring. 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spellingShingle	Vock Vita M misc RC346-429 misc Neurology. Diseases of the nervous system A forward genetic screen with a thalamocortical axon reporter mouse yields novel neurodevelopment mutants and a distinct <it<emx2 </it<mutant phenotype
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topic_title	RC346-429 A forward genetic screen with a thalamocortical axon reporter mouse yields novel neurodevelopment mutants and a distinct <it<emx2 </it<mutant phenotype
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title	A forward genetic screen with a thalamocortical axon reporter mouse yields novel neurodevelopment mutants and a distinct <it<emx2 </it<mutant phenotype
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title_full	A forward genetic screen with a thalamocortical axon reporter mouse yields novel neurodevelopment mutants and a distinct <it<emx2 </it<mutant phenotype
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title_sort	forward genetic screen with a thalamocortical axon reporter mouse yields novel neurodevelopment mutants and a distinct <it<emx2 </it<mutant phenotype
callnumber	RC346-429
title_auth	A forward genetic screen with a thalamocortical axon reporter mouse yields novel neurodevelopment mutants and a distinct <it<emx2 </it<mutant phenotype
abstract	<p<Abstract</p< <p<Background</p< <p<The dorsal thalamus acts as a gateway and modulator for information going to and from the cerebral cortex. This activity requires the formation of reciprocal topographic axon connections between thalamus and cortex. The axons grow along a complex multistep pathway, making sharp turns, crossing expression boundaries, and encountering intermediate targets. However, the cellular and molecular components mediating these steps remain poorly understood.</p< <p<Results</p< <p<To further elucidate the development of the thalamocortical system, we first created a thalamocortical axon reporter line to use as a genetic tool for sensitive analysis of mutant mouse phenotypes. The TCA-<it<tau-lacZ </it<reporter mouse shows specific, robust, and reproducible labeling of thalamocortical axons (TCAs), but not the overlapping corticothalamic axons, during development. Moreover, it readily reveals TCA pathfinding abnormalities in known cortical mutants such as <it<reeler</it<. Next, we performed an unbiased screen for genes involved in thalamocortical development using random mutagenesis with the TCA reporter. Six independent mutant lines show aberrant TCA phenotypes at different steps of the pathway. These include ventral misrouting, overfasciculation, stalling at the corticostriatal boundary, and invasion of ectopic cortical cell clusters. An outcross breeding strategy coupled with a genomic panel of single nucleotide polymorphisms facilitated genetic mapping with small numbers of mutant mice. We mapped a ventral misrouting mutant to the <it<Emx2 </it<gene, and discovered that some TCAs extend to the olfactory bulbs in this mutant. Mapping data suggest that other lines carry mutations in genes not previously known for roles in thalamocortical development.</p< <p<Conclusions</p< <p<These data demonstrate the feasibility of a forward genetic approach to understanding mammalian brain morphogenesis and wiring. A robust axonal reporter enabled sensitive analysis of a specific axon tract inside the mouse brain, identifying mutant phenotypes at multiple steps of the pathway, and revealing a new aspect of the <it<Emx2 </it<mutant. The phenotypes highlight vulnerable choice points and latent tendencies of TCAs, and will lead to a refined understanding of the elements and interactions required to form the thalamocortical system.</p< <p<See Commentary: <url<http://www.biomedcentral.com/1741-7007/9/1</url<</p<
abstractGer	<p<Abstract</p< <p<Background</p< <p<The dorsal thalamus acts as a gateway and modulator for information going to and from the cerebral cortex. This activity requires the formation of reciprocal topographic axon connections between thalamus and cortex. The axons grow along a complex multistep pathway, making sharp turns, crossing expression boundaries, and encountering intermediate targets. However, the cellular and molecular components mediating these steps remain poorly understood.</p< <p<Results</p< <p<To further elucidate the development of the thalamocortical system, we first created a thalamocortical axon reporter line to use as a genetic tool for sensitive analysis of mutant mouse phenotypes. The TCA-<it<tau-lacZ </it<reporter mouse shows specific, robust, and reproducible labeling of thalamocortical axons (TCAs), but not the overlapping corticothalamic axons, during development. Moreover, it readily reveals TCA pathfinding abnormalities in known cortical mutants such as <it<reeler</it<. Next, we performed an unbiased screen for genes involved in thalamocortical development using random mutagenesis with the TCA reporter. Six independent mutant lines show aberrant TCA phenotypes at different steps of the pathway. These include ventral misrouting, overfasciculation, stalling at the corticostriatal boundary, and invasion of ectopic cortical cell clusters. An outcross breeding strategy coupled with a genomic panel of single nucleotide polymorphisms facilitated genetic mapping with small numbers of mutant mice. We mapped a ventral misrouting mutant to the <it<Emx2 </it<gene, and discovered that some TCAs extend to the olfactory bulbs in this mutant. Mapping data suggest that other lines carry mutations in genes not previously known for roles in thalamocortical development.</p< <p<Conclusions</p< <p<These data demonstrate the feasibility of a forward genetic approach to understanding mammalian brain morphogenesis and wiring. A robust axonal reporter enabled sensitive analysis of a specific axon tract inside the mouse brain, identifying mutant phenotypes at multiple steps of the pathway, and revealing a new aspect of the <it<Emx2 </it<mutant. The phenotypes highlight vulnerable choice points and latent tendencies of TCAs, and will lead to a refined understanding of the elements and interactions required to form the thalamocortical system.</p< <p<See Commentary: <url<http://www.biomedcentral.com/1741-7007/9/1</url<</p<
abstract_unstemmed	<p<Abstract</p< <p<Background</p< <p<The dorsal thalamus acts as a gateway and modulator for information going to and from the cerebral cortex. This activity requires the formation of reciprocal topographic axon connections between thalamus and cortex. The axons grow along a complex multistep pathway, making sharp turns, crossing expression boundaries, and encountering intermediate targets. However, the cellular and molecular components mediating these steps remain poorly understood.</p< <p<Results</p< <p<To further elucidate the development of the thalamocortical system, we first created a thalamocortical axon reporter line to use as a genetic tool for sensitive analysis of mutant mouse phenotypes. The TCA-<it<tau-lacZ </it<reporter mouse shows specific, robust, and reproducible labeling of thalamocortical axons (TCAs), but not the overlapping corticothalamic axons, during development. Moreover, it readily reveals TCA pathfinding abnormalities in known cortical mutants such as <it<reeler</it<. Next, we performed an unbiased screen for genes involved in thalamocortical development using random mutagenesis with the TCA reporter. Six independent mutant lines show aberrant TCA phenotypes at different steps of the pathway. These include ventral misrouting, overfasciculation, stalling at the corticostriatal boundary, and invasion of ectopic cortical cell clusters. An outcross breeding strategy coupled with a genomic panel of single nucleotide polymorphisms facilitated genetic mapping with small numbers of mutant mice. We mapped a ventral misrouting mutant to the <it<Emx2 </it<gene, and discovered that some TCAs extend to the olfactory bulbs in this mutant. Mapping data suggest that other lines carry mutations in genes not previously known for roles in thalamocortical development.</p< <p<Conclusions</p< <p<These data demonstrate the feasibility of a forward genetic approach to understanding mammalian brain morphogenesis and wiring. A robust axonal reporter enabled sensitive analysis of a specific axon tract inside the mouse brain, identifying mutant phenotypes at multiple steps of the pathway, and revealing a new aspect of the <it<Emx2 </it<mutant. The phenotypes highlight vulnerable choice points and latent tendencies of TCAs, and will lead to a refined understanding of the elements and interactions required to form the thalamocortical system.</p< <p<See Commentary: <url<http://www.biomedcentral.com/1741-7007/9/1</url<</p<
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title_short	A forward genetic screen with a thalamocortical axon reporter mouse yields novel neurodevelopment mutants and a distinct <it<emx2 </it<mutant phenotype
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A forward genetic screen with a thalamocortical axon reporter mouse yields novel neurodevelopment mutants and a distinct <it<emx2 </it<mutant phenotype

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