PMID- 23701883 OWN - NLM STAT- MEDLINE DCOM- 20130910 LR - 20190605 IS - 1095-564X (Electronic) IS - 0012-1606 (Linking) VI - 380 IP - 2 DP - 2013 Aug 15 TI - Temporal regulation of single-minded target genes in the ventral midline of the Drosophila central nervous system. PG - 335-43 LID - S0012-1606(13)00260-1 [pii] LID - 10.1016/j.ydbio.2013.05.015 [doi] AB - Differentiation of a specific organ or tissue requires sequential activation of regulatory genes. However, little is known about how serial gene expression is temporally regulated. Here, we present evidence that differential expression of single-minded (sim) target genes can be attributed, in part, to the number of Sim and Tango (Tgo) heterodimer binding sites within their enhancer regions. The Sim, termed a master regulator, directs ventral midline differentiation of Drosophila central nervous system (CNS). According to data on the onset timing of ventral midline gene expression, sim target genes are classified into at least 2 groups (early and late). The sim and rhomboid (rho) genes are activated during early midline differentiation whereas orthodenticle (otd), CG10249, and slit (sli) genes undergo activation during later stages of midline differentiation. Germline transformation and in situ hybridization with transgenic embryos demonstrate that enhancers activating sim and rho expression contain 4 Sim-Tgo binding sites whereas only 1 Sim-Tgo binding site is found in an enhancer of sli. A mutagenized version of the rho enhancer lacking either 1, 2, or 3 Sim-Tgo binding sites mediated progressively more delayed expression of a lacZ reporter gene in the ventral midline. In contrast, a modified sli enhancer displayed progressively earlier onset of lacZ expression when 1, 2, or 3 more Sim-Tgo binding sites were added. Taken together, these results suggest that the number of Sim-Tgo-binding sites is decisive in determining the timing of gene expression in the developing ventral midline. We also discuss a combinatorial model accounting for the sequential expression of sim target genes. CI - Copyright (c) 2013 Elsevier Inc. All rights reserved. FAU - Hong, Joung-Woo AU - Hong JW AD - Graduate School of East-West Medical Science, Kyung Hee University, Yongin 446-701, South Korea. jwhong46@khu.ac.kr FAU - Park, Kye Won AU - Park KW FAU - Levine, Michael S AU - Levine MS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130520 PL - United States TA - Dev Biol JT - Developmental biology JID - 0372762 RN - 0 (Basic Helix-Loop-Helix Transcription Factors) RN - 0 (Drosophila Proteins) RN - 0 (Membrane Proteins) RN - 0 (Nuclear Proteins) RN - 0 (Rho protein, Drosophila) RN - 0 (sim protein, Drosophila) RN - 0 (tgo protein, Drosophila) RN - 138391-32-9 (Aryl Hydrocarbon Receptor Nuclear Translocator) SB - IM MH - Animals MH - Aryl Hydrocarbon Receptor Nuclear Translocator/genetics MH - Basic Helix-Loop-Helix Transcription Factors/*genetics MH - Binding Sites MH - Cell Differentiation MH - Central Nervous System/*embryology MH - Drosophila Proteins/*genetics MH - Drosophila melanogaster/*embryology MH - *Gene Expression Regulation, Developmental MH - Membrane Proteins/genetics MH - Nuclear Proteins/*genetics MH - SELEX Aptamer Technique OTO - NOTNLM OT - Drosophila OT - Embryo OT - Single-minded OT - Temporal regulation OT - Ventral midline EDAT- 2013/05/25 06:00 MHDA- 2013/09/11 06:00 CRDT- 2013/05/25 06:00 PHST- 2013/03/14 00:00 [received] PHST- 2013/05/11 00:00 [revised] PHST- 2013/05/13 00:00 [accepted] PHST- 2013/05/25 06:00 [entrez] PHST- 2013/05/25 06:00 [pubmed] PHST- 2013/09/11 06:00 [medline] AID - S0012-1606(13)00260-1 [pii] AID - 10.1016/j.ydbio.2013.05.015 [doi] PST - ppublish SO - Dev Biol. 2013 Aug 15;380(2):335-43. doi: 10.1016/j.ydbio.2013.05.015. Epub 2013 May 20.