title: The Drosophila gap gene giant regulates ecdysone production through specification of the PTTH-producing neurons.
abstract: In Drosophila melanogaster, hypomorphic mutations in the gap gene giant (gt) have long been known to affect ecdysone titers resulting in developmental delay and the production of large (giant) larvae, pupae and adults. However, the mechanism by which gt regulates ecdysone production has remained elusive. Here we show that hypomorphic gt mutations lead to ecdysone deficiency and developmental delay by affecting the specification of the PG neurons that produce prothoracicotropic hormone (PTTH). The gt¹ hypomorphic mutation leads to random loss of PTTH production in one or more of the 4 PG neurons in the larval brain. In cases where PTTH production is lost in all four PG neurons, delayed development and giant larvae are produced. Since immunostaining shows no evidence for Gt expression in the PG neurons once PTTH production is detectable, it is unlikely that Gt directly regulates PTTH expression. Instead, we find that innervation of the prothoracic gland by the PG neurons is absent in gt hypomorphic larvae that do not express PTTH. In addition, PG neuron axon fasciculation is abnormal in many gt hypomorphic larvae. Since several other anteriorly expressed gap genes such as tailless and orthodenticle have previously been found to affect the fate of the cerebral labrum, a region of the brain that gives rise to the neuroendocrine cells that innervate the ring gland, we conclude that gt likely controls ecdysone production indirectly by contributing the peptidergic phenotype of the PTTH-producing neurons in the embryo.
authors.affiliation: Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Arpan
authors.initials: A
authors.lastname: Ghosh
authors.forename: Zofeyah
authors.initials: Z
authors.lastname: McBrayer
authors.forename: Michael B
authors.initials: MB
authors.lastname: O'Connor
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D019521:Body Patterning / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D004440:Ecdysone / Q000096:biosynthesis*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D007301:Insect Hormones / Q000096:biosynthesis*; D008297:Male; D008959:Models, Neurological; D009154:Mutation; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D029721:Drosophila Proteins; D007301:Insect Hormones; D012097:Repressor Proteins; C118475:gt protein, Drosophila; D004440:Ecdysone; C009089:prothoracicotropic hormone
references.citation: Genetics. 2007 Nov;177(3):1667-77
references.pmid: 17947427
references.citation: Dev Biol. 1987 Jan;119(1):175-89
references.pmid: 3098602
references.citation: Development. 2003 Nov;130(22):5457-70
references.pmid: 14507784
references.citation: Science. 1991 Nov 29;254(5036):1385-7
references.pmid: 1683715
references.citation: Development. 1992 Jan;114(1):99-112
references.pmid: 1576969
references.citation: Annu Rev Entomol. 2002;47:883-916
references.pmid: 11729094
references.citation: Dev Biol. 2007 Feb 1;302(1):309-23
references.pmid: 17070515
references.citation: Dev Cell. 2007 Dec;13(6):857-71
references.pmid: 18061567
references.citation: Bioessays. 2007 Apr;29(4):344-55
references.pmid: 17373657
references.citation: Dev Biol. 2003 Sep 1;261(1):1-9
references.pmid: 12941617
references.citation: Cell. 2003 Apr 4;113(1):73-86
references.pmid: 12679036
references.citation: J Morphol. 1969 Oct;129(2):171-99
references.pmid: 5356774
references.citation: Biochim Biophys Acta. 2007 Aug;1773(8):1263-84
references.pmid: 17126425
references.citation: Science. 2009 Dec 4;326(5958):1403-5
references.pmid: 19965758
references.citation: Nat Rev Genet. 2006 Dec;7(12):907-16
references.pmid: 17139322
references.citation: Dev Biol. 1997 Feb 15;182(2):270-83
references.pmid: 9070327
references.citation: EMBO J. 1989 May;8(5):1539-48
references.pmid: 2504582
references.citation: Development. 1991 Feb;111(2):367-78
references.pmid: 1716553
references.citation: Dev Biol. 1985 Jun;109(2):321-35
references.pmid: 3996753
references.citation: J Comp Neurol. 2001 Mar 19;431(4):481-91
references.pmid: 11223816
references.citation: Dev Biol. 1990 Jul;140(1):57-72
references.pmid: 1972684
references.citation: Dev Biol. 1984 May;103(1):85-95
references.pmid: 6425099
references.citation: Insect Biochem Mol Biol. 1994 Feb;24(2):175-89
references.pmid: 8111426