A regulatory network to segregate the identity of neuronal subtypes.
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.
Department of Molecular Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA. sklee@bcm.edu
Seunghee
S
Lee
Bora
B
Lee
Kaumudi
K
Joshi
Samuel L
SL
Pfaff
Jae W
JW
Lee
Soo-Kyung
SK
Lee
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001369:Axons / Q000502:physiology; D002642:Chick Embryo; D018274:Electroporation; D018507:Gene Expression Regulation, Developmental / Q000235:genetics* / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D007395:Interneurons / Q000145:classification / Q000166:cytology / Q000502:physiology*; D060588:LIM Domain Proteins; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008954:Models, Biological; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000145:classification / Q000166:cytology / Q000502:physiology*; D020218:Response Elements / Q000235:genetics; D052156:SELEX Aptamer Technique; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; C491976:Lmo4 protein, mouse; D014157:Transcription Factors; C088975:Vsx2 protein, mouse; C084059:Hb9 protein, mouse