PMID- 21945234 OWN - NLM STAT- MEDLINE DCOM- 20120224 LR - 20211020 IS - 1872-7298 (Electronic) IS - 1567-133X (Print) IS - 1567-133X (Linking) VI - 11 IP - 8 DP - 2011 Dec TI - Molecular and functional analysis of Drosophila single-minded larval central brain expression. PG - 533-46 LID - 10.1016/j.gep.2011.09.002 [doi] AB - Developmental regulatory proteins are commonly utilized in multiple cell types throughout development. The Drosophila single-minded (sim) gene acts as master regulator of embryonic CNS midline cell development and transcription. However, it is also expressed in the brain during larval development. In this paper, we demonstrate that sim is expressed in three clusters of anterior central brain neurons: DAMv1/2, BAmas1/2, and TRdm and in three clusters of posterior central brain neurons: a subset of DPM neurons, and two previously unidentified clusters, which we term PLSC and PSC. In addition, sim is expressed in the lamina and medulla of the optic lobes. MARCM studies confirm that sim is expressed at high levels in neurons but is low or absent in neuroblasts (NBs) and ganglion mother cell (GMC) precursors. In the anterior brain, sim(+) neurons are detected in 1st and 2nd instar larvae but rapidly increase in number during the 3rd instar stage. To understand the regulation of sim brain transcription, 12 fragments encompassing 5'-flanking, intronic, and 3'-flanking regions were tested for the presence of enhancers that drive brain expression of a reporter gene. Three of these fragments drove expression in sim(+) brain cells, including all sim(+) neuronal clusters in the central brain and optic lobes. One fragment upstream of sim is autoregulatory and is expressed in all sim(+) brain cells. One intronic fragment drives expression in only the PSC and laminar neurons. Another downstream intronic fragment drives expression in all sim(+) brain neurons, except the PSC and lamina. Thus, together these two enhancers drive expression in all sim(+) brain neurons. Sequence analysis of existing sim mutant alleles identified three likely null alleles to utilize in MARCM experiments to examine sim brain function. Mutant clones of DAMv1/2 neurons revealed a consistent axonal fasciculation defect. Thus, unlike the embryonic roles of sim that control CNS midline neuron and glial formation and differentiation, postembryonic sim, instead, controls aspects of axon guidance in the brain. This resembles the roles of vertebrate sim that have an early role in neuronal migration and a later role in axonogenesis. CI - Copyright (c) 2011 Elsevier B.V. All rights reserved. FAU - Freer, Stephanie M AU - Freer SM AD - Department of Biochemistry and Biophysics, Program in Molecular Biology and Biotechnology, The University of North Carolina at Chapel Hill, NC 27599-3280, USA. FAU - Lau, Daniel C AU - Lau DC FAU - Pearson, Joseph C AU - Pearson JC FAU - Talsky, Kristin Benjamin AU - Talsky KB FAU - Crews, Stephen T AU - Crews ST LA - eng GR - R01 NS075079/NS/NINDS NIH HHS/United States GR - R37 HD025251-23/HD/NICHD NIH HHS/United States GR - R37 HD025251/HD/NICHD NIH HHS/United States GR - S10 RR021055-01/RR/NCRR NIH HHS/United States GR - T32 HD046369/HD/NICHD NIH HHS/United States GR - S10 RR021055/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20110914 PL - Netherlands TA - Gene Expr Patterns JT - Gene expression patterns : GEP JID - 101167473 RN - 0 (Drosophila Proteins) RN - 0 (Nerve Tissue Proteins) SB - IM MH - Animals MH - Brain/cytology/*embryology MH - Drosophila Proteins/*biosynthesis MH - Drosophila melanogaster MH - Embryo, Nonmammalian/cytology/*embryology MH - Gene Expression Regulation, Developmental/*physiology MH - Larva/cytology/metabolism MH - Nerve Tissue Proteins/*biosynthesis MH - Neurons/cytology/metabolism MH - Transcription, Genetic/*physiology PMC - PMC3200459 MID - NIHMS325620 EDAT- 2011/09/29 06:00 MHDA- 2012/03/01 06:00 PMCR- 2012/12/01 CRDT- 2011/09/28 06:00 PHST- 2011/08/10 00:00 [received] PHST- 2011/09/06 00:00 [accepted] PHST- 2011/09/28 06:00 [entrez] PHST- 2011/09/29 06:00 [pubmed] PHST- 2012/03/01 06:00 [medline] PHST- 2012/12/01 00:00 [pmc-release] AID - S1567-133X(11)00087-1 [pii] AID - 10.1016/j.gep.2011.09.002 [doi] PST - ppublish SO - Gene Expr Patterns. 2011 Dec;11(8):533-46. doi: 10.1016/j.gep.2011.09.002. Epub 2011 Sep 14.