A Regulatory Network to Segregate the Identity of Neuronal Subtypes

Seunghee Lee; Bora Lee; Kaumudi Joshi; Samuel L. Pfaff; Jae W. Lee; Soo Kyung Lee

doi:10.1016/j.devcel.2008.03.021

A Regulatory Network to Segregate the Identity of Neuronal Subtypes

Seunghee Lee
, Bora Lee
, Kaumudi Joshi
, Samuel L. Pfaff
, Jae W. Lee
, Soo Kyung Lee

Research output: Contribution to journal › Article › peer-review

100 Scopus citations

Abstract

Spinal motor neurons (MNs) and V2 interneurons (V2-INs) are specified by two related LIM-complexes, MN-hexamer and V2-tetramer, respectively. Here we show how multiple parallel and complementary feedback loops are integrated to assign these two cell fates accurately. While MN-hexamer response elements (REs) are specific to MN-hexamer, V2-tetramer-REs can bind both LIM-complexes. In embryonic MNs, however, two factors cooperatively suppress the aberrant activation of V2-tetramer-REs. First, LMO4 blocks V2-tetramer assembly. Second, MN-hexamer induces a repressor, Hb9, which binds V2-tetramer-REs and suppresses their activation. V2-INs use a similar approach; V2-tetramer induces a repressor, Chx10, which binds MN-hexamer-REs and blocks their activation. Thus, our study uncovers a regulatory network to segregate related cell fates, which involves reciprocal feedforward gene regulatory loops.

Original language	English (US)
Pages (from-to)	877-889
Number of pages	13
Journal	Developmental Cell
Volume	14
Issue number	6
DOIs	https://doi.org/10.1016/j.devcel.2008.03.021
State	Published - Jun 10 2008
Externally published	Yes

Funding

We thank Hugo Bellen and Adam Antebi for critically reading the manuscript, Hilda Puente and Jae Kim for technical assistance, and Rod Bremner for Chx10 vectors. This research was supported by grants from NINDS (R01 NS054941), PEW, March of Dimes Foundations, and MRDDRC P30 HD24064.

Funders	Funder number
MRDDRC	P30 HD24064
National Institute of Neurological Disorders and Stroke	R01 NS054941, R01NS054172
March of Dimes Foundation

Keywords

DEVBIO

ASJC Scopus subject areas

Molecular Biology
General Biochemistry, Genetics and Molecular Biology
Developmental Biology
Cell Biology

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10.1016/j.devcel.2008.03.021

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@article{7466990688024b65a66493979b57053b,

title = "A Regulatory Network to Segregate the Identity of Neuronal Subtypes",

abstract = "Spinal motor neurons (MNs) and V2 interneurons (V2-INs) are specified by two related LIM-complexes, MN-hexamer and V2-tetramer, respectively. Here we show how multiple parallel and complementary feedback loops are integrated to assign these two cell fates accurately. While MN-hexamer response elements (REs) are specific to MN-hexamer, V2-tetramer-REs can bind both LIM-complexes. In embryonic MNs, however, two factors cooperatively suppress the aberrant activation of V2-tetramer-REs. First, LMO4 blocks V2-tetramer assembly. Second, MN-hexamer induces a repressor, Hb9, which binds V2-tetramer-REs and suppresses their activation. V2-INs use a similar approach; V2-tetramer induces a repressor, Chx10, which binds MN-hexamer-REs and blocks their activation. Thus, our study uncovers a regulatory network to segregate related cell fates, which involves reciprocal feedforward gene regulatory loops.",

keywords = "DEVBIO",

author = "Seunghee Lee and Bora Lee and Kaumudi Joshi and Pfaff, \{Samuel L.\} and Lee, \{Jae W.\} and Lee, \{Soo Kyung\}",

note = "Funding Information: We thank Hugo Bellen and Adam Antebi for critically reading the manuscript, Hilda Puente and Jae Kim for technical assistance, and Rod Bremner for Chx10 vectors. This research was supported by grants from NINDS (R01 NS054941), PEW, March of Dimes Foundations, and MRDDRC P30 HD24064. ",

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doi = "10.1016/j.devcel.2008.03.021",

language = "English (US)",

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AU - Lee, Seunghee

AU - Lee, Bora

AU - Joshi, Kaumudi

AU - Pfaff, Samuel L.

AU - Lee, Jae W.

AU - Lee, Soo Kyung

N1 - Funding Information: We thank Hugo Bellen and Adam Antebi for critically reading the manuscript, Hilda Puente and Jae Kim for technical assistance, and Rod Bremner for Chx10 vectors. This research was supported by grants from NINDS (R01 NS054941), PEW, March of Dimes Foundations, and MRDDRC P30 HD24064.

PY - 2008/6/10

Y1 - 2008/6/10

N2 - Spinal motor neurons (MNs) and V2 interneurons (V2-INs) are specified by two related LIM-complexes, MN-hexamer and V2-tetramer, respectively. Here we show how multiple parallel and complementary feedback loops are integrated to assign these two cell fates accurately. While MN-hexamer response elements (REs) are specific to MN-hexamer, V2-tetramer-REs can bind both LIM-complexes. In embryonic MNs, however, two factors cooperatively suppress the aberrant activation of V2-tetramer-REs. First, LMO4 blocks V2-tetramer assembly. Second, MN-hexamer induces a repressor, Hb9, which binds V2-tetramer-REs and suppresses their activation. V2-INs use a similar approach; V2-tetramer induces a repressor, Chx10, which binds MN-hexamer-REs and blocks their activation. Thus, our study uncovers a regulatory network to segregate related cell fates, which involves reciprocal feedforward gene regulatory loops.

AB - Spinal motor neurons (MNs) and V2 interneurons (V2-INs) are specified by two related LIM-complexes, MN-hexamer and V2-tetramer, respectively. Here we show how multiple parallel and complementary feedback loops are integrated to assign these two cell fates accurately. While MN-hexamer response elements (REs) are specific to MN-hexamer, V2-tetramer-REs can bind both LIM-complexes. In embryonic MNs, however, two factors cooperatively suppress the aberrant activation of V2-tetramer-REs. First, LMO4 blocks V2-tetramer assembly. Second, MN-hexamer induces a repressor, Hb9, which binds V2-tetramer-REs and suppresses their activation. V2-INs use a similar approach; V2-tetramer induces a repressor, Chx10, which binds MN-hexamer-REs and blocks their activation. Thus, our study uncovers a regulatory network to segregate related cell fates, which involves reciprocal feedforward gene regulatory loops.

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JO - Developmental Cell

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IS - 6

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A Regulatory Network to Segregate the Identity of Neuronal Subtypes

Abstract

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Keywords

ASJC Scopus subject areas

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