Psychiatry related information on emc

• This indicates that the zebrafish gene described here is a genuine member of the Id family, and suggests that it may serve a function similar to that of the Drosophila gene emc and mammalian Ids during development [1].

High impact information on emc

• While neither h nor emc is required for photoreceptor cell determination, in emc-h-clones the morphogenetic furrow and differentiated eye field advance up to eight ommatidial rows ahead of adjacent wild-type tissue [2].
• We propose a model in which the emc protein negatively regulates sensory organ determination by forming heterodimers with the HLH proteins encoded by the AS-C and/or daughterless, thereby altering or interfering with their activity [3].
• The emc protein shares the dimerization domain of other HLH proteins but lacks their DNA binding motif [3].
• The tam mutation reduces the transcription of a repressor gene, extramacrochaetae, and causes enlargement of a proneural cluster where supernumerary precursor cells emerge, resulting in extra mechanosensory organs in the fly [4].
• Spatial regulation of proneural gene activity: auto- and cross-activation of achaete is antagonized by extramacrochaetae [5].

Biological context of emc

• As currently thought, this seems accomplished by heterodimerization via the HLH domain, because an amino acid substitution in this region abolishes the emc antagonistic effect both in vitro and in vivo [6].
• We show that, during embryonic development, the extramacrochaetae gene is expressed in complex patterns that comprise derivatives of the three embryonic layers [7].
• Neural fate specification in Drosophila is promoted by the products of the proneural genes, such as those of the achaete-scute complex, and antagonized by the products of the Enhancer of split [E(spl)] complex, hairy, and extramacrochaetae [8].
• Mutations at some candidate loci (bb, emc, h, Dl, Hairless) showed strong interactions with selected chromosomes, whereas others interacted weakly (ASC, abd, Scr) or not at all (N, mab, E(spl)) [9].
• In addition, cell proliferation behaviour of emc mutant cells varies depending on the mutant background [10].

Anatomical context of emc

• extramacrochaetae (emc) functions during many developmental processes in Drosophila, such as sensory organ formation, sex determination, wing vein differentiation, regulation of eye photoreceptor differentiation, cell proliferation and development of the Malpighian tubules, trachea and muscles in the embryo [11].
• Genetic and molecular characterization of these candidate lines reveals that some loci identified in this screen correspond to genes known to function in the formation of the peripheral nervous system, such as big brain, extra macrochaetae, and numb [12].

Physical interactions of emc

• The Drosophila extramacrochaetae protein antagonizes sequence-specific DNA binding by daughterless/achaete-scute protein complexes [13].
• Down regulation of extramacrochaetae mRNA by a Drosophila neural RNA binding protein Rbp9 which is homologous to human Hu proteins [14].

Regulatory relationships of emc

• We propose that at least during vein differentiation and wing margin formation, extramacrochaetae is regulated by Notch and collaborates with other Notch-downstream genes such as Enhancer of split-m(beta) [15].
• The known proneural antagonists either titrate these proteins by forming inactive complexes (extramacrochaetae) or repress achaete/scute expression at specific sites (i.e., hairy) [16].

Other interactions of emc

• When one of these spatial restrictions is eliminated, by ubiquitously expressing ac-sc, SMCs still emerge within minima of emc [17].
• Within the ectodermal layer, its level is neither elevated (as in the case of AS-C genes) nor reduced (as in the case of emc product) in the proneural cluster [18].
• These results suggest that negative regulation by emc may be a common feature of developmental processes involving da, the AS-C and possibly other helix-loop-helix proteins [19].
• Synergistic interactions between pyd and Notch, Delta and extramacrochaetae mutations support this model [20].
• Thus, loss-of-function conditions for ed give rise to the development of extra macrochaetae near the extant ones and increase the density of microchaetae [21].

Analytical, diagnostic and therapeutic context of emc

• Our results strongly support the model of negative regulation of emc on ac and sc transcription through titration of their products [6].

References