A switch in numb isoforms is a critical step in cortical development
Loss of numb function suggests that numb maintains progenitors in an undifferentiated state. Herein, we demonstrate that numb1 and numb3 are expressed in undifferentiated cortical progenitors, whereas numb2 and numb4 become prominent throughout differentiation. To further assess the role of differen...
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Veröffentlicht in: | Developmental dynamics 2007-03, Vol.236 (3), p.696-705 |
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creator | Bani‐Yaghoub, Mahmud Kubu, Chris J. Cowling, Rebecca Rochira, Jennifer Nikopoulos, George N. Bellum, Stephen Verdi, Joseph M. |
description | Loss of numb function suggests that numb maintains progenitors in an undifferentiated state. Herein, we demonstrate that numb1 and numb3 are expressed in undifferentiated cortical progenitors, whereas numb2 and numb4 become prominent throughout differentiation. To further assess the role of different numb isoforms in cortical neural development, we first created a Numb‐null state with antisense morpholino, followed by the re‐expression of specific numb isoforms. The re‐expression of numb1 or numb3 resulted in a significant reduction of neural differentiation, correlating with an expansion of the cortical progenitor pool. In contrast, the expression of numb2 or numb4 resulted in a reduction of proliferating progenitors and a corresponding increase in mammalian achete‐scute homologue (MASH1) expression, concurrent with the appearance of the mitogen‐activated protein‐2–positive neurons. Of interest, the effect of numb isoforms on neural differentiation could not be directly related to Notch, because classic canonical Notch signaling assays failed to uncover any differences in the four isoforms to inhibit the Notch downstream events. This finding suggests that numb may have other signaling properties during neuronal differentiation in addition to augmenting notch signal strength. Developmental Dynamics 236:696–705, 2007. © 2007 Wiley‐Liss, Inc. |
doi_str_mv | 10.1002/dvdy.21072 |
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Herein, we demonstrate that numb1 and numb3 are expressed in undifferentiated cortical progenitors, whereas numb2 and numb4 become prominent throughout differentiation. To further assess the role of different numb isoforms in cortical neural development, we first created a Numb‐null state with antisense morpholino, followed by the re‐expression of specific numb isoforms. The re‐expression of numb1 or numb3 resulted in a significant reduction of neural differentiation, correlating with an expansion of the cortical progenitor pool. In contrast, the expression of numb2 or numb4 resulted in a reduction of proliferating progenitors and a corresponding increase in mammalian achete‐scute homologue (MASH1) expression, concurrent with the appearance of the mitogen‐activated protein‐2–positive neurons. Of interest, the effect of numb isoforms on neural differentiation could not be directly related to Notch, because classic canonical Notch signaling assays failed to uncover any differences in the four isoforms to inhibit the Notch downstream events. This finding suggests that numb may have other signaling properties during neuronal differentiation in addition to augmenting notch signal strength. Developmental Dynamics 236:696–705, 2007. © 2007 Wiley‐Liss, Inc.</description><identifier>ISSN: 1058-8388</identifier><identifier>EISSN: 1097-0177</identifier><identifier>DOI: 10.1002/dvdy.21072</identifier><identifier>PMID: 17253625</identifier><language>eng</language><publisher>New York: Wiley‐Liss, Inc</publisher><subject>Animals ; Basic Helix-Loop-Helix Transcription Factors - genetics ; Basic Helix-Loop-Helix Transcription Factors - metabolism ; Blotting, Western ; Cell Differentiation - genetics ; Cell Differentiation - physiology ; Cells, Cultured ; differentiation ; Embryonic Development - genetics ; Embryonic Development - physiology ; Gene Expression Regulation, Developmental ; Immunohistochemistry ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Membrane Proteins - physiology ; Mice ; Nerve Tissue Proteins - genetics ; Nerve Tissue Proteins - metabolism ; Nerve Tissue Proteins - physiology ; neurogenesis ; Neurons - cytology ; Neurons - metabolism ; notch ; numb ; Oligonucleotides, Antisense - genetics ; Protein Isoforms - genetics ; Protein Isoforms - metabolism ; Protein Isoforms - physiology ; Receptors, Notch - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; self‐renewal</subject><ispartof>Developmental dynamics, 2007-03, Vol.236 (3), p.696-705</ispartof><rights>Copyright © 2007 Wiley‐Liss, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4602-5d6a4d36c695a7e574de259720ca05beb2c987f0f45459ccae1f619e49c820493</citedby><cites>FETCH-LOGICAL-c4602-5d6a4d36c695a7e574de259720ca05beb2c987f0f45459ccae1f619e49c820493</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fdvdy.21072$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fdvdy.21072$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17253625$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bani‐Yaghoub, Mahmud</creatorcontrib><creatorcontrib>Kubu, Chris J.</creatorcontrib><creatorcontrib>Cowling, Rebecca</creatorcontrib><creatorcontrib>Rochira, Jennifer</creatorcontrib><creatorcontrib>Nikopoulos, George N.</creatorcontrib><creatorcontrib>Bellum, Stephen</creatorcontrib><creatorcontrib>Verdi, Joseph M.</creatorcontrib><title>A switch in numb isoforms is a critical step in cortical development</title><title>Developmental dynamics</title><addtitle>Dev Dyn</addtitle><description>Loss of numb function suggests that numb maintains progenitors in an undifferentiated state. Herein, we demonstrate that numb1 and numb3 are expressed in undifferentiated cortical progenitors, whereas numb2 and numb4 become prominent throughout differentiation. To further assess the role of different numb isoforms in cortical neural development, we first created a Numb‐null state with antisense morpholino, followed by the re‐expression of specific numb isoforms. The re‐expression of numb1 or numb3 resulted in a significant reduction of neural differentiation, correlating with an expansion of the cortical progenitor pool. In contrast, the expression of numb2 or numb4 resulted in a reduction of proliferating progenitors and a corresponding increase in mammalian achete‐scute homologue (MASH1) expression, concurrent with the appearance of the mitogen‐activated protein‐2–positive neurons. Of interest, the effect of numb isoforms on neural differentiation could not be directly related to Notch, because classic canonical Notch signaling assays failed to uncover any differences in the four isoforms to inhibit the Notch downstream events. This finding suggests that numb may have other signaling properties during neuronal differentiation in addition to augmenting notch signal strength. Developmental Dynamics 236:696–705, 2007. © 2007 Wiley‐Liss, Inc.</description><subject>Animals</subject><subject>Basic Helix-Loop-Helix Transcription Factors - genetics</subject><subject>Basic Helix-Loop-Helix Transcription Factors - metabolism</subject><subject>Blotting, Western</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Differentiation - physiology</subject><subject>Cells, Cultured</subject><subject>differentiation</subject><subject>Embryonic Development - genetics</subject><subject>Embryonic Development - physiology</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Immunohistochemistry</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Membrane Proteins - physiology</subject><subject>Mice</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Nerve Tissue Proteins - physiology</subject><subject>neurogenesis</subject><subject>Neurons - cytology</subject><subject>Neurons - metabolism</subject><subject>notch</subject><subject>numb</subject><subject>Oligonucleotides, Antisense - genetics</subject><subject>Protein Isoforms - genetics</subject><subject>Protein Isoforms - metabolism</subject><subject>Protein Isoforms - physiology</subject><subject>Receptors, Notch - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>self‐renewal</subject><issn>1058-8388</issn><issn>1097-0177</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMtKw0AUQAdRbK1u_ADJyoWQemcyj8yytL6g4EYFV8NkMsGRPOpM0tK_NzEFd7q6l8vhwD0IXWKYYwBym2_z_ZxgEOQITTFIEQMW4njYWRqnSZpO0FkInwCQcopP0QQLwhJO2BStFlHYudZ8RK6O6q7KIheaovFV6JdIR8a71hldRqG1m4ExjR8Pud3astlUtm7P0Umhy2AvDnOGXu_vXpaP8fr54Wm5WMeGciAxy7mmecINl0wLywTNLWFSEDAaWGYzYmQqCigoo0waoy0uOJaWSpMSoDKZoevRu_HNV2dDqyoXjC1LXdumC0oAwRQ4_Av2Nty_n_TgzQga34TgbaE23lXa7xUGNcRVQ1z1E7eHrw7WLqts_oseavYAHoGdK-3-D5Vava3eR-k37_iDcA</recordid><startdate>200703</startdate><enddate>200703</enddate><creator>Bani‐Yaghoub, Mahmud</creator><creator>Kubu, Chris J.</creator><creator>Cowling, Rebecca</creator><creator>Rochira, Jennifer</creator><creator>Nikopoulos, George N.</creator><creator>Bellum, Stephen</creator><creator>Verdi, Joseph M.</creator><general>Wiley‐Liss, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>200703</creationdate><title>A switch in numb isoforms is a critical step in cortical development</title><author>Bani‐Yaghoub, Mahmud ; Kubu, Chris J. ; Cowling, Rebecca ; Rochira, Jennifer ; Nikopoulos, George N. ; Bellum, Stephen ; Verdi, Joseph M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4602-5d6a4d36c695a7e574de259720ca05beb2c987f0f45459ccae1f619e49c820493</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animals</topic><topic>Basic Helix-Loop-Helix Transcription Factors - genetics</topic><topic>Basic Helix-Loop-Helix Transcription Factors - metabolism</topic><topic>Blotting, Western</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Differentiation - physiology</topic><topic>Cells, Cultured</topic><topic>differentiation</topic><topic>Embryonic Development - genetics</topic><topic>Embryonic Development - physiology</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Immunohistochemistry</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Membrane Proteins - physiology</topic><topic>Mice</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Nerve Tissue Proteins - physiology</topic><topic>neurogenesis</topic><topic>Neurons - cytology</topic><topic>Neurons - metabolism</topic><topic>notch</topic><topic>numb</topic><topic>Oligonucleotides, Antisense - genetics</topic><topic>Protein Isoforms - genetics</topic><topic>Protein Isoforms - metabolism</topic><topic>Protein Isoforms - physiology</topic><topic>Receptors, Notch - metabolism</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>self‐renewal</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bani‐Yaghoub, Mahmud</creatorcontrib><creatorcontrib>Kubu, Chris J.</creatorcontrib><creatorcontrib>Cowling, Rebecca</creatorcontrib><creatorcontrib>Rochira, Jennifer</creatorcontrib><creatorcontrib>Nikopoulos, George N.</creatorcontrib><creatorcontrib>Bellum, Stephen</creatorcontrib><creatorcontrib>Verdi, Joseph M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Developmental dynamics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bani‐Yaghoub, Mahmud</au><au>Kubu, Chris J.</au><au>Cowling, Rebecca</au><au>Rochira, Jennifer</au><au>Nikopoulos, George N.</au><au>Bellum, Stephen</au><au>Verdi, Joseph M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A switch in numb isoforms is a critical step in cortical development</atitle><jtitle>Developmental dynamics</jtitle><addtitle>Dev Dyn</addtitle><date>2007-03</date><risdate>2007</risdate><volume>236</volume><issue>3</issue><spage>696</spage><epage>705</epage><pages>696-705</pages><issn>1058-8388</issn><eissn>1097-0177</eissn><abstract>Loss of numb function suggests that numb maintains progenitors in an undifferentiated state. Herein, we demonstrate that numb1 and numb3 are expressed in undifferentiated cortical progenitors, whereas numb2 and numb4 become prominent throughout differentiation. To further assess the role of different numb isoforms in cortical neural development, we first created a Numb‐null state with antisense morpholino, followed by the re‐expression of specific numb isoforms. The re‐expression of numb1 or numb3 resulted in a significant reduction of neural differentiation, correlating with an expansion of the cortical progenitor pool. In contrast, the expression of numb2 or numb4 resulted in a reduction of proliferating progenitors and a corresponding increase in mammalian achete‐scute homologue (MASH1) expression, concurrent with the appearance of the mitogen‐activated protein‐2–positive neurons. Of interest, the effect of numb isoforms on neural differentiation could not be directly related to Notch, because classic canonical Notch signaling assays failed to uncover any differences in the four isoforms to inhibit the Notch downstream events. This finding suggests that numb may have other signaling properties during neuronal differentiation in addition to augmenting notch signal strength. Developmental Dynamics 236:696–705, 2007. © 2007 Wiley‐Liss, Inc.</abstract><cop>New York</cop><pub>Wiley‐Liss, Inc</pub><pmid>17253625</pmid><doi>10.1002/dvdy.21072</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Basic Helix-Loop-Helix Transcription Factors - genetics Basic Helix-Loop-Helix Transcription Factors - metabolism Blotting, Western Cell Differentiation - genetics Cell Differentiation - physiology Cells, Cultured differentiation Embryonic Development - genetics Embryonic Development - physiology Gene Expression Regulation, Developmental Immunohistochemistry Membrane Proteins - genetics Membrane Proteins - metabolism Membrane Proteins - physiology Mice Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Nerve Tissue Proteins - physiology neurogenesis Neurons - cytology Neurons - metabolism notch numb Oligonucleotides, Antisense - genetics Protein Isoforms - genetics Protein Isoforms - metabolism Protein Isoforms - physiology Receptors, Notch - metabolism Reverse Transcriptase Polymerase Chain Reaction self‐renewal |
title | A switch in numb isoforms is a critical step in cortical development |
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