Uncoupling Dendrite Growth and Patterning: Single-Cell Knockout Analysis of NMDA Receptor 2B
N-methyl-D-aspartate receptors (NMDARs) play important functions in neural development. NR2B is the predominant NR2 subunit of NMDAR in the developing brain. Here we use mosaic analysis with double markers (MADM) to knock out NR2B in isolated single cells and analyze its cell-autonomous function in...
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| Veröffentlicht in: | Neuron (Cambridge, Mass.) Mass.), 2009-04, Vol.62 (2), p.205-217 |
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| creator | Espinosa, J. Sebastian Wheeler, Damian G. Tsien, Richard W. Luo, Liqun |
| description | N-methyl-D-aspartate receptors (NMDARs) play important functions in neural development. NR2B is the predominant NR2 subunit of NMDAR in the developing brain. Here we use mosaic analysis with double markers (MADM) to knock out NR2B in isolated single cells and analyze its cell-autonomous function in dendrite development. NR2B mutant dentate gyrus granule cells (dGCs) and barrel cortex layer 4 spiny stellate cells (bSCs) have similar dendritic growth rates, total length, and branch number as control cells. However, mutant dGCs maintain supernumerary primary dendrites resulting from a pruning defect. Furthermore, while control bSCs restrict dendritic growth to a single barrel, mutant bSCs maintain dendritic growth in multiple barrels. Thus, NR2B functions cell autonomously to regulate dendrite patterning to ensure that sensory information is properly represented in the cortex. Our study also indicates that molecular mechanisms that regulate activity-dependent dendrite patterning can be separated from those that control general dendrite growth and branching. |
| doi_str_mv | 10.1016/j.neuron.2009.03.006 |
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Sebastian ; Wheeler, Damian G. ; Tsien, Richard W. ; Luo, Liqun</creator><creatorcontrib>Espinosa, J. Sebastian ; Wheeler, Damian G. ; Tsien, Richard W. ; Luo, Liqun</creatorcontrib><description>N-methyl-D-aspartate receptors (NMDARs) play important functions in neural development. NR2B is the predominant NR2 subunit of NMDAR in the developing brain. Here we use mosaic analysis with double markers (MADM) to knock out NR2B in isolated single cells and analyze its cell-autonomous function in dendrite development. NR2B mutant dentate gyrus granule cells (dGCs) and barrel cortex layer 4 spiny stellate cells (bSCs) have similar dendritic growth rates, total length, and branch number as control cells. However, mutant dGCs maintain supernumerary primary dendrites resulting from a pruning defect. Furthermore, while control bSCs restrict dendritic growth to a single barrel, mutant bSCs maintain dendritic growth in multiple barrels. Thus, NR2B functions cell autonomously to regulate dendrite patterning to ensure that sensory information is properly represented in the cortex. Our study also indicates that molecular mechanisms that regulate activity-dependent dendrite patterning can be separated from those that control general dendrite growth and branching.</description><identifier>ISSN: 0896-6273</identifier><identifier>EISSN: 1097-4199</identifier><identifier>DOI: 10.1016/j.neuron.2009.03.006</identifier><identifier>PMID: 19409266</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Age Factors ; Animals ; Animals, Newborn ; Body Patterning - genetics ; Calcium - metabolism ; Cell Count ; CELLBIO ; Cerebral Cortex - cytology ; Dendrites - drug effects ; Dendrites - physiology ; Dentate Gyrus - cytology ; Deoxyuridine ; DEVBIO ; Embryo, Mammalian ; Gene Expression Regulation, Developmental ; Green Fluorescent Proteins - genetics ; Mice ; Mice, Knockout ; Models, Biological ; MOLNEURO ; Neurons ; Neurons - classification ; Neurons - cytology ; Neurons - drug effects ; Neurons - physiology ; Phosphopyruvate Hydratase - metabolism ; Receptors, N-Methyl-D-Aspartate - deficiency ; Receptors, N-Methyl-D-Aspartate - genetics ; Receptors, N-Methyl-D-Aspartate - physiology ; Rodents</subject><ispartof>Neuron (Cambridge, Mass.), 2009-04, Vol.62 (2), p.205-217</ispartof><rights>2009 Elsevier Inc.</rights><rights>Copyright Elsevier Limited Apr 30, 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c555t-e8291feb0f52b3750fb4ce43cde0360b18d7334771b8ebdad8861d979f029de63</citedby><cites>FETCH-LOGICAL-c555t-e8291feb0f52b3750fb4ce43cde0360b18d7334771b8ebdad8861d979f029de63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0896627309002050$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19409266$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Espinosa, J. Sebastian</creatorcontrib><creatorcontrib>Wheeler, Damian G.</creatorcontrib><creatorcontrib>Tsien, Richard W.</creatorcontrib><creatorcontrib>Luo, Liqun</creatorcontrib><title>Uncoupling Dendrite Growth and Patterning: Single-Cell Knockout Analysis of NMDA Receptor 2B</title><title>Neuron (Cambridge, Mass.)</title><addtitle>Neuron</addtitle><description>N-methyl-D-aspartate receptors (NMDARs) play important functions in neural development. NR2B is the predominant NR2 subunit of NMDAR in the developing brain. Here we use mosaic analysis with double markers (MADM) to knock out NR2B in isolated single cells and analyze its cell-autonomous function in dendrite development. NR2B mutant dentate gyrus granule cells (dGCs) and barrel cortex layer 4 spiny stellate cells (bSCs) have similar dendritic growth rates, total length, and branch number as control cells. However, mutant dGCs maintain supernumerary primary dendrites resulting from a pruning defect. 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| subjects | Age Factors Animals Animals, Newborn Body Patterning - genetics Calcium - metabolism Cell Count CELLBIO Cerebral Cortex - cytology Dendrites - drug effects Dendrites - physiology Dentate Gyrus - cytology Deoxyuridine DEVBIO Embryo, Mammalian Gene Expression Regulation, Developmental Green Fluorescent Proteins - genetics Mice Mice, Knockout Models, Biological MOLNEURO Neurons Neurons - classification Neurons - cytology Neurons - drug effects Neurons - physiology Phosphopyruvate Hydratase - metabolism Receptors, N-Methyl-D-Aspartate - deficiency Receptors, N-Methyl-D-Aspartate - genetics Receptors, N-Methyl-D-Aspartate - physiology Rodents |
| title | Uncoupling Dendrite Growth and Patterning: Single-Cell Knockout Analysis of NMDA Receptor 2B |
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