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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Developmental dynamics 2007-03, Vol.236 (3), p.696-705
Hauptverfasser: Bani‐Yaghoub, Mahmud, Kubu, Chris J., Cowling, Rebecca, Rochira, Jennifer, Nikopoulos, George N., Bellum, Stephen, Verdi, Joseph M.
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 705
container_issue 3
container_start_page 696
container_title Developmental dynamics
container_volume 236
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
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_70214060</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>20416253</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4602-5d6a4d36c695a7e574de259720ca05beb2c987f0f45459ccae1f619e49c820493</originalsourceid><addsrcrecordid>eNqFkMtKw0AUQAdRbK1u_ADJyoWQemcyj8yytL6g4EYFV8NkMsGRPOpM0tK_NzEFd7q6l8vhwD0IXWKYYwBym2_z_ZxgEOQITTFIEQMW4njYWRqnSZpO0FkInwCQcopP0QQLwhJO2BStFlHYudZ8RK6O6q7KIheaovFV6JdIR8a71hldRqG1m4ExjR8Pud3astlUtm7P0Umhy2AvDnOGXu_vXpaP8fr54Wm5WMeGciAxy7mmecINl0wLywTNLWFSEDAaWGYzYmQqCigoo0waoy0uOJaWSpMSoDKZoevRu_HNV2dDqyoXjC1LXdumC0oAwRQ4_Av2Nty_n_TgzQga34TgbaE23lXa7xUGNcRVQ1z1E7eHrw7WLqts_oseavYAHoGdK-3-D5Vava3eR-k37_iDcA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>20416253</pqid></control><display><type>article</type><title>A switch in numb isoforms is a critical step in cortical development</title><source>MEDLINE</source><source>Wiley Online Library Free Content</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Wiley Online Library All Journals</source><source>Alma/SFX Local Collection</source><creator>Bani‐Yaghoub, Mahmud ; Kubu, Chris J. ; Cowling, Rebecca ; Rochira, Jennifer ; Nikopoulos, George N. ; Bellum, Stephen ; Verdi, Joseph M.</creator><creatorcontrib>Bani‐Yaghoub, Mahmud ; Kubu, Chris J. ; Cowling, Rebecca ; Rochira, Jennifer ; Nikopoulos, George N. ; Bellum, Stephen ; Verdi, Joseph M.</creatorcontrib><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><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>
fulltext fulltext
identifier ISSN: 1058-8388
ispartof Developmental dynamics, 2007-03, Vol.236 (3), p.696-705
issn 1058-8388
1097-0177
language eng
recordid cdi_proquest_miscellaneous_70214060
source MEDLINE; Wiley Online Library Free Content; EZB-FREE-00999 freely available EZB journals; Wiley Online Library All Journals; Alma/SFX Local Collection
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
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-28T02%3A15%3A58IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20switch%20in%20numb%20isoforms%20is%20a%20critical%20step%20in%20cortical%20development&rft.jtitle=Developmental%20dynamics&rft.au=Bani%E2%80%90Yaghoub,%20Mahmud&rft.date=2007-03&rft.volume=236&rft.issue=3&rft.spage=696&rft.epage=705&rft.pages=696-705&rft.issn=1058-8388&rft.eissn=1097-0177&rft_id=info:doi/10.1002/dvdy.21072&rft_dat=%3Cproquest_cross%3E20416253%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=20416253&rft_id=info:pmid/17253625&rfr_iscdi=true