TY - JOUR
T1 - A Regulatory Network to Segregate the Identity of Neuronal Subtypes
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.
KW - DEVBIO
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U2 - 10.1016/j.devcel.2008.03.021
DO - 10.1016/j.devcel.2008.03.021
M3 - Article
C2 - 18539116
AN - SCOPUS:44449163364
SN - 1534-5807
VL - 14
SP - 877
EP - 889
JO - Developmental Cell
JF - Developmental Cell
IS - 6
ER -