Two Genetically and Molecularly Distinct Functions Involved in Early Neurogenesis Reside Within the Enhancer of split Locus of Drosophila melanogaster

INVESTIGATIONS

Two Genetically and Molecularly Distinct Functions Involved in Early Neurogenesis Reside Within the Enhancer of split Locus of Drosophila melanogaster

C. Delidakis, A. Preiss, D. A. Hartley and S. Artavanis-Tsakonas
Howard Hughes Medical Institute, Departments of Cell Biology and Biology, Yale University, New Haven Connecticut 06511

Molecular correlation of the genetic aspects of the function of the neurogenic gene Enhancer of split [E(spl)] has previously been hampered by the densely transcribed nature of the chromosomal region within which it resides. We present data indicating that two distinct molecular species contribute to E(spl) function. Analysis of new E(spl) alleles has allowed us to define two complementing functions within the locus. Subsequent phenotypic analysis of different E(spl) deficiencies combined with P element-transformed constructs has demonstrated that these two functions correspond to: (1) a family of helix-loop-helix (HLH) protein-encoding genes and (2) the single copy gene E(spl) m9/10, whose product shares homology with G-protein {beta} subunits. The zygotically active E(spl) HLH genes can, at least partially, substitute for one another's functions and their total copy number determines the activity of the locus. E(spl) m9/10 acts synergistically with the E(spl) HLH genes and other neurogenic genes in the process of neurogenesis. The maternal component of E(spl) m9/10 has the most pronounced effect in neurogenesis, while its zygotic component is predominantly required during postembryonic development. The lethality of trans-heterozygotes of null E(spl) deficiency alleles with a strong Delta point mutation is a result of the concomitant reduction in activity of both E(spl) HLH and m9/10 functions. Immunocytochemical localization of the E(spl) m9/10 protein has revealed that it is a ubiquitously distributed nuclear component in embryonic, larval and imaginal tissues.

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				G. Jiménez, A. Guichet, A. Ephrussi, and J. Casanova Relief of gene repression by Torso RTK signaling: role of capicua in Drosophila terminal and dorsoventral patterning Genes & Dev., January 15, 2000; 14(2): 224 - 231. [Abstract] [Full Text]

				E. Lai, R Bodner, and J. Posakony The enhancer of split complex of Drosophila includes four Notch-regulated members of the bearded gene family Development, January 8, 2000; 127(16): 3441 - 3455. [Abstract] [PDF]

				E. Lai, R Bodner, J Kavaler, G Freschi, and J. Posakony Antagonism of notch signaling activity by members of a novel protein family encoded by the bearded and enhancer of split gene complexes Development, January 1, 2000; 127(2): 291 - 306. [Abstract] [PDF]

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				J. de Celis, J de Celis, P Ligoxygakis, A Preiss, C Delidakis, and S Bray Functional relationships between Notch, Su(H) and the bHLH genes of the E(spl) complex: the E(spl) genes mediate only a subset of Notch activities during imaginal development Development, January 9, 1996; 122(9): 2719 - 2728. [Abstract] [PDF]

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				S Artavanis-Tsakonas, K Matsuno, and M. Fortini Notch signaling Science, April 14, 1995; 268(5208): 225 - 232. [Abstract] [PDF]

				K Matsuno, R. Diederich, M. Go, C. Blaumueller, and S Artavanis-Tsakonas Deltex acts as a positive regulator of Notch signaling through interactions with the Notch ankyrin repeats Development, January 8, 1995; 121(8): 2633 - 2644. [Abstract] [PDF]

				A Singson, M W Leviten, A G Bang, X H Hua, and J W Posakony Direct downstream targets of proneural activators in the imaginal disc include genes involved in lateral inhibitory signaling. Genes & Dev., September 1, 1994; 8(17): 2058 - 2071. [Abstract] [PDF]

				B Jennings, A Preiss, C Delidakis, and S Bray The Notch signalling pathway is required for Enhancer of split bHLH protein expression during neurogenesis in the Drosophila embryo Development, January 12, 1994; 120(12): 3537 - 3548. [Abstract] [PDF]

				R. Diederich, K Matsuno, H Hing, and S Artavanis-Tsakonas Cytosolic interaction between deltex and Notch ankyrin repeats implicates deltex in the Notch signaling pathway Development, January 3, 1994; 120(3): 473 - 481. [Abstract] [PDF]

				K. W. McLarren, F. M. Theriault, and S. Stifani Association with the Nuclear Matrix and Interaction with Groucho and RUNX Proteins Regulate the Transcription Repression Activity of the Basic Helix Loop Helix Factor Hes1 J. Biol. Chem., January 5, 2001; 276(2): 1578 - 1584. [Abstract] [Full Text] [PDF]