Rnf220 cooperates with Zc4h2 to specify spinal progenitor domains [RESEARCH ARTICLE]

Kim, J., Choi, T.-I., Park, S., Kim, M. H., Kim, C.-H., Lee, S.
The Company of Biologists
Published 2018
Publication Date:
2018-09-16
Publisher:
The Company of Biologists
Print ISSN:
0950-1991
Electronic ISSN:
1477-9129
Topics:
Biology
Published by:
_version_ 1836399051287822336
autor Kim, J., Choi, T.-I., Park, S., Kim, M. H., Kim, C.-H., Lee, S.
beschreibung Jumee Kim, Tae-Ik Choi, Shinhye Park, Myung Hee Kim, Cheol-Hee Kim, and Seunghee Lee During early embryonic development of the spinal cord, graded sonic hedgehog signaling establishes distinct ventral progenitor domains by regulating the spatiotemporal expression of fate-specifying transcription factors. However, regulation of their protein stability remains incompletely understood. Here, we show that RNF220, an E3 ubiquitin ligase, plays crucial roles in the generation of the ventral progenitor domains, which produce ventral interneurons and motor neurons, by targeting key transcription factors including Dbx1/2 and Nkx2.2 for degradation. Surprisingly, RNF220 interacts with, and is co-expressed with, a zinc-finger protein ZC4H2, and they cooperate to degrade Dbx1/2 and Nkx2.2. RNF220-null mice show widespread alterations of ventral progenitor domains, including the loss of the p2 domain that produces V2 interneurons. Knockdown of RNF220 and ZC4H2 in the chick spinal cord downregulates expression of the V2 interneuronal marker Chx10. Co-expression of RNF220 and ZC4H2 further promotes the ability of Nkx6.1 to induce ectopic Chx10 + V2 interneurons. Our results uncover a novel regulatory pathway in establishing distinct progenitor domains through modulating the protein stability of transcription factors. Our results provide insights into the molecular mechanism by which ZC4H2 mutations lead to human syndromes characterized by delayed motor development.
citation_standardnr 6333114
datenlieferant ipn_articles
feed_id 1748
feed_publisher The Company of Biologists
feed_publisher_url http://www.biologists.com/
insertion_date 2018-09-16
journaleissn 1477-9129
journalissn 0950-1991
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher The Company of Biologists
quelle Development
relation http://dev.biologists.org/cgi/content/short/145/17/dev165340?rss=1
search_space articles
shingle_author_1 Kim, J., Choi, T.-I., Park, S., Kim, M. H., Kim, C.-H., Lee, S.
shingle_author_2 Kim, J., Choi, T.-I., Park, S., Kim, M. H., Kim, C.-H., Lee, S.
shingle_author_3 Kim, J., Choi, T.-I., Park, S., Kim, M. H., Kim, C.-H., Lee, S.
shingle_author_4 Kim, J., Choi, T.-I., Park, S., Kim, M. H., Kim, C.-H., Lee, S.
shingle_catch_all_1 Rnf220 cooperates with Zc4h2 to specify spinal progenitor domains [RESEARCH ARTICLE]
Jumee Kim, Tae-Ik Choi, Shinhye Park, Myung Hee Kim, Cheol-Hee Kim, and Seunghee Lee During early embryonic development of the spinal cord, graded sonic hedgehog signaling establishes distinct ventral progenitor domains by regulating the spatiotemporal expression of fate-specifying transcription factors. However, regulation of their protein stability remains incompletely understood. Here, we show that RNF220, an E3 ubiquitin ligase, plays crucial roles in the generation of the ventral progenitor domains, which produce ventral interneurons and motor neurons, by targeting key transcription factors including Dbx1/2 and Nkx2.2 for degradation. Surprisingly, RNF220 interacts with, and is co-expressed with, a zinc-finger protein ZC4H2, and they cooperate to degrade Dbx1/2 and Nkx2.2. RNF220-null mice show widespread alterations of ventral progenitor domains, including the loss of the p2 domain that produces V2 interneurons. Knockdown of RNF220 and ZC4H2 in the chick spinal cord downregulates expression of the V2 interneuronal marker Chx10. Co-expression of RNF220 and ZC4H2 further promotes the ability of Nkx6.1 to induce ectopic Chx10 + V2 interneurons. Our results uncover a novel regulatory pathway in establishing distinct progenitor domains through modulating the protein stability of transcription factors. Our results provide insights into the molecular mechanism by which ZC4H2 mutations lead to human syndromes characterized by delayed motor development.
Kim, J., Choi, T.-I., Park, S., Kim, M. H., Kim, C.-H., Lee, S.
The Company of Biologists
0950-1991
09501991
1477-9129
14779129
shingle_catch_all_2 Rnf220 cooperates with Zc4h2 to specify spinal progenitor domains [RESEARCH ARTICLE]
Jumee Kim, Tae-Ik Choi, Shinhye Park, Myung Hee Kim, Cheol-Hee Kim, and Seunghee Lee During early embryonic development of the spinal cord, graded sonic hedgehog signaling establishes distinct ventral progenitor domains by regulating the spatiotemporal expression of fate-specifying transcription factors. However, regulation of their protein stability remains incompletely understood. Here, we show that RNF220, an E3 ubiquitin ligase, plays crucial roles in the generation of the ventral progenitor domains, which produce ventral interneurons and motor neurons, by targeting key transcription factors including Dbx1/2 and Nkx2.2 for degradation. Surprisingly, RNF220 interacts with, and is co-expressed with, a zinc-finger protein ZC4H2, and they cooperate to degrade Dbx1/2 and Nkx2.2. RNF220-null mice show widespread alterations of ventral progenitor domains, including the loss of the p2 domain that produces V2 interneurons. Knockdown of RNF220 and ZC4H2 in the chick spinal cord downregulates expression of the V2 interneuronal marker Chx10. Co-expression of RNF220 and ZC4H2 further promotes the ability of Nkx6.1 to induce ectopic Chx10 + V2 interneurons. Our results uncover a novel regulatory pathway in establishing distinct progenitor domains through modulating the protein stability of transcription factors. Our results provide insights into the molecular mechanism by which ZC4H2 mutations lead to human syndromes characterized by delayed motor development.
Kim, J., Choi, T.-I., Park, S., Kim, M. H., Kim, C.-H., Lee, S.
The Company of Biologists
0950-1991
09501991
1477-9129
14779129
shingle_catch_all_3 Rnf220 cooperates with Zc4h2 to specify spinal progenitor domains [RESEARCH ARTICLE]
Jumee Kim, Tae-Ik Choi, Shinhye Park, Myung Hee Kim, Cheol-Hee Kim, and Seunghee Lee During early embryonic development of the spinal cord, graded sonic hedgehog signaling establishes distinct ventral progenitor domains by regulating the spatiotemporal expression of fate-specifying transcription factors. However, regulation of their protein stability remains incompletely understood. Here, we show that RNF220, an E3 ubiquitin ligase, plays crucial roles in the generation of the ventral progenitor domains, which produce ventral interneurons and motor neurons, by targeting key transcription factors including Dbx1/2 and Nkx2.2 for degradation. Surprisingly, RNF220 interacts with, and is co-expressed with, a zinc-finger protein ZC4H2, and they cooperate to degrade Dbx1/2 and Nkx2.2. RNF220-null mice show widespread alterations of ventral progenitor domains, including the loss of the p2 domain that produces V2 interneurons. Knockdown of RNF220 and ZC4H2 in the chick spinal cord downregulates expression of the V2 interneuronal marker Chx10. Co-expression of RNF220 and ZC4H2 further promotes the ability of Nkx6.1 to induce ectopic Chx10 + V2 interneurons. Our results uncover a novel regulatory pathway in establishing distinct progenitor domains through modulating the protein stability of transcription factors. Our results provide insights into the molecular mechanism by which ZC4H2 mutations lead to human syndromes characterized by delayed motor development.
Kim, J., Choi, T.-I., Park, S., Kim, M. H., Kim, C.-H., Lee, S.
The Company of Biologists
0950-1991
09501991
1477-9129
14779129
shingle_catch_all_4 Rnf220 cooperates with Zc4h2 to specify spinal progenitor domains [RESEARCH ARTICLE]
Jumee Kim, Tae-Ik Choi, Shinhye Park, Myung Hee Kim, Cheol-Hee Kim, and Seunghee Lee During early embryonic development of the spinal cord, graded sonic hedgehog signaling establishes distinct ventral progenitor domains by regulating the spatiotemporal expression of fate-specifying transcription factors. However, regulation of their protein stability remains incompletely understood. Here, we show that RNF220, an E3 ubiquitin ligase, plays crucial roles in the generation of the ventral progenitor domains, which produce ventral interneurons and motor neurons, by targeting key transcription factors including Dbx1/2 and Nkx2.2 for degradation. Surprisingly, RNF220 interacts with, and is co-expressed with, a zinc-finger protein ZC4H2, and they cooperate to degrade Dbx1/2 and Nkx2.2. RNF220-null mice show widespread alterations of ventral progenitor domains, including the loss of the p2 domain that produces V2 interneurons. Knockdown of RNF220 and ZC4H2 in the chick spinal cord downregulates expression of the V2 interneuronal marker Chx10. Co-expression of RNF220 and ZC4H2 further promotes the ability of Nkx6.1 to induce ectopic Chx10 + V2 interneurons. Our results uncover a novel regulatory pathway in establishing distinct progenitor domains through modulating the protein stability of transcription factors. Our results provide insights into the molecular mechanism by which ZC4H2 mutations lead to human syndromes characterized by delayed motor development.
Kim, J., Choi, T.-I., Park, S., Kim, M. H., Kim, C.-H., Lee, S.
The Company of Biologists
0950-1991
09501991
1477-9129
14779129
shingle_title_1 Rnf220 cooperates with Zc4h2 to specify spinal progenitor domains [RESEARCH ARTICLE]
shingle_title_2 Rnf220 cooperates with Zc4h2 to specify spinal progenitor domains [RESEARCH ARTICLE]
shingle_title_3 Rnf220 cooperates with Zc4h2 to specify spinal progenitor domains [RESEARCH ARTICLE]
shingle_title_4 Rnf220 cooperates with Zc4h2 to specify spinal progenitor domains [RESEARCH ARTICLE]
timestamp 2025-06-30T23:36:49.411Z
titel Rnf220 cooperates with Zc4h2 to specify spinal progenitor domains [RESEARCH ARTICLE]
titel_suche Rnf220 cooperates with Zc4h2 to specify spinal progenitor domains [RESEARCH ARTICLE]
topic W
uid ipn_articles_6333114