Identification of target genes of the homeotic gene Antennapedia by enhancer detection

©1991 by Cold Spring Harbor LaboratoryDOI: 10.1101/gad.5.12b.2467Localized expression of the homeotic gene Antennapedia (Antp) in Drosophila melanogaster is required for normal development of the thoracic segments. When the Antp gene is expressed ectopically in the larval primordium of the antenna, the antennal imaginal disc, the developmental fate of the disc is switched and the adult antenna is transformed to a mesothoracic leg. We screened approximately 550 different fly strains carrying single copies of an enhancer-detector transposon to identify regulatory elements and corresponding genes that are either activated or repressed in antennal discs in response to this transformation. Several regulatory elements that are either direct or indirect targets of Antp were found. One transposant that expresses the reporter gene (lacZ) in the antennal disc, but not in the leg disc, was studied in more detail. The enhancer detector in this strain is located near a similarly regulated gene at the spalt (sal) locus, which encodes a homeotic function involved in embryonic head and tail development. The expression of this newly discovered gene, spalt major (salm) is strongly repressed in gain-of-function mutants that express Antp in the antennal disc. Recessive loss-of-function mutations (Antp-) have the opposite developmental effect; they cause the differentiation of antennal structures in the second leg disc. Accordingly, salm is derepressed in clones of homozygous Antp- cells. Therefore, we conclude that Antp negatively regulates salm. The time course of the interaction and reporter gene fusion experiments suggests (but does not prove) a direct interaction between Antp and cis-regulatory elements of salm. Our analysis of several enhancer-detector strains suggests that the basic patterning information in the antennal and leg imaginal discs is very similar

csal1 Is Controlled by a Combination of FGF and Wnt Signals in Developing Limb Buds

While some of the signaling molecules that govern establishment of the limb axis have been characterized, little is known about the downstream effector genes that interpret these signals. In Drosophila, the spalt gene is involved in cell fate determination and pattern formation in different tissues. We have cloned a chick homologue of Drosophila spalt, which we have termed csal1, and this study focuses on the regulation of csal1 expression in the limb bud. csal1 is expressed in limb buds from HH 17 to 26, in both the apical ectodermal ridge and the distal mesenchyme. Signals from the apical ridge are essential for csal1 expression, while the dorsal ectoderm is required for csal1 expression at a distance from the ridge. Our data indicate that both FGF and Wnt signals are required for the regulation of csal1 expression in the limb. Mutations in the human homologue of csal1, termed Hsal1/SALL1, result in a condition known as Townes–Brocks syndrome (TBS), which is characterized by preaxial polydactyly. The developmental expression of csal1 together with the digit phenotype in TBS patients suggests that csal1 may play a role in some aspects of distal patterning

Institutional interactions and economic growth: The joint effects of property rights, veto players and democratic capital

We investigate the possible interaction effects that the extent of property rights protection and separation of powers in a political system have on economic growth. Using analysis of panel data from more than countries over the period 1970-2010 we find that the growth effects of property rights increase when political power is divided among more veto players. When distinguishing between institutional veto players (political institutions) and partisan veto players (fractionalization among political parties), we further find that the growth effects of property rights are driven mainly by checks on the chief executive (in bicameral systems) and primarily found in countries with large stocks of democratic capital

spalt encodes an evolutionarily conserved zinc finger protein of novel structure which provides homeotic gene function in the head and tail region of the Drosophila embryo.

The region specific homeotic gene spalt (sal) of Drosophila melanogaster promotes the specification of terminal pattern elements as opposed to segments in the trunk. Our results show that the previously reported sal transcription unit was misidentified. Based on P-element mediated germ line transformation and DNA sequence analysis of sal mutant alleles, we identified the transcription unit that carries sal function. sal is located close to the misidentified transcription unit, and it is expressed in similar temporal and spatial patterns during embryogenesis. The sal gene encodes a zinc finger protein of novel structure composed of three widely spaced 'double zinc finger' motifs of internally conserved sequences and a single zinc finger motif of different sequence. Antibodies produced against the sal protein show that sal is first expressed at the blastoderm stage and later in restricted areas of the embryonic nervous system as well as in the developing trachea. The antibodies detect sal homologous proteins in corresponding spatial and temporal patterns in the embryos of related insect species. Sequence analysis of the sal gene of Drosophila virilis, a species which is phylogenetically separated by approximately 60 million years, suggests that the sal function is conserved during evolution, consistent with its proposed role in head formation during arthropod evolution

Drosophila spalt/spalt-related mutants exhibit Townes-Brocks' syndrome phenotypes

Mutations in SALL1, the human homolog of the Drosophila spalt gene, result in Townes-Brocks' syndrome, which is characterized by hand/foot, anogenital, renal, and ear anomalies, including sensorineural deafness. spalt genes encode zinc finger transcription factors that are found in animals as diverse as worms, insects, and vertebrates. Here, we examine the effect of losing both of the spalt genes, spalt and spalt-related, in the fruit fly Drosophila melanogaster, and report defects similar to those in humans with Townes-Brocks' syndrome. Loss of both spalt and spalt-related function in flies yields morphological defects in the testes, genitalia, and the antenna. Furthermore, spalt/spalt-related mutant antennae show severe reductions in Johnston's organ, the major auditory organ in Drosophila. Electrophysiological analyses confirm that spalt/spalt-related mutant flies are deaf. These commonalities suggest that there is functional conservation for spalt genes between vertebrates and insects