Disease relevance of ap

• In ap loss-of-function mutants, some of the protocerebral and deutocerebral interneurons that express Ap in the wild type show axon pathfinding errors and fasciculation defects in the brain, notably in the fascicles of the brain commissure [1].
• Mutations at the apterous (ap) locus in Drosophila melanogaster give rise to three distinct phenotypes: aberrant wings, female sterility and precocious adult death [2].
• A strain of Drosophila melanogaster carrying a mutation in the apterous gene (ap4) was known to exhibit arrested vitellogenesis (rescuable by applying exogenous juvenile hormone), sterility of both sexes, and a deficiency of juvenile hormone [3].

High impact information on ap

• This signal acts together with apterous and squeeze to activate FMRFamide expression [4].
• In 3T3 fibroblasts, the same LIM proteins prevent phorbol ester-induced inhibition of DNA replication [5].
• We report here that spatially localized expression of the homeobox gene apterous (ap) specifies the identity of dorsal cells in the wing [6].
• The boundary of cell lineage restriction between dorsal and ventral compartments coincides with the limit of the domain of ap expression [6].
• However, ap expression also regulates signalling between dorsal and ventral compartments, resulting in high levels of Notch signalling at the D/V boundary [7].

Biological context of ap

• Moreover, we were able to rescue the muscle phenotype of vg(null) flies by using the activity of ap promoter to drive VG expression [8].
• Moreover, we observed an ectopic expression of ct and ap, two markers of DFM development, in developing IFMs of vg(null) pupae [8].
• CONCLUSION: Normal cell proliferation is necessary for ap expression at the level of the D/V boundary [9].
• Control of apterous by vestigial drives indirect flight muscle development in Drosophila [8].
• In Drosophila three LIM homeobox genes, apterous, lim3 and isl, have been shown to control axon pathfinding of subsets of neurons within the embryo [10].

Anatomical context of ap

• The wing is subdivided into dorsal (D) and ventral (V) compartments by the activity of the selector gene apterous in D cells [11].
• The nature of the defects in homozygous null mutant flies is consistent with the pattern of ap expression in the larval imaginal discs. ap is also expressed in a complex pattern in the embryo, including portions of the peripheral nervous system (PNS) and central nervous system (CNS) [12].
• In contrast, the interneurons that project to the ring gland do not appear to be affected in ap mutants [1].
• Within the Pannier domain of expression, Pannier and Apterous may compete for binding to their common Chip cofactor, and the accurate stoichiometry between these three proteins is essential for both proneural prepattern and compartmentalization of the thorax [13].
• We show that the direct flight muscles are specified by the expression of Apterous, a Lim homeodomain protein, in groups of myoblasts [14].

Associations of ap with chemical compounds

• The deduced amino acid sequence of ap predicts a homeo domain and a cysteine/histidine-rich domain known as the LIM domain [12].
• Mlp60A encodes a protein with a single LIM domain linked to a glycine-rich region [15].
• The evolutionarily conserved LIM protein PINCH is postulated to act as part of an integrin-dependent signaling complex [16].
• The latter characterized by a unique histidine residue in the zinc binding motif (C2HC5 and C3HC4 for the LIM and RING respectively) may constitute protein/protein interaction interfaces [17].

Regulatory relationships of ap

• Early VG product regulates AP activity by inducing dLMO and thus indirectly regulating ap target genes such as fringe and the PSalpha1 and PSalpha2 integrins [9].
• We provide evidence that ap ectopic expression can induce per se ectopic twi expression and muscle degeneration [8].
• The LIM-HD protein Apterous has been shown to regulate expression of the FMRFamide neuropeptide in Drosophila neurons (Benveniste et al. [1998] Development 125:4757-4765) [18].
• Beadex encodes an LMO protein that regulates Apterous LIM-homeodomain activity in Drosophila wing development: a model for LMO oncogene function [19].
• We provide evidence that, at the onset of wing development, Delta is under the control of apterous and might be the Notch ligand in this process [20].

Other interactions of ap

• We report the cloning of a LIM-containing gene from Drosophila, termed Dlmo, which is highly homologous to the vertebrate LIM-only (LMO) genes [21].
• Neurosecretory identity conferred by the apterous gene: lateral horn leucokinin neurons in Drosophila [18].
• Here we describe the isolation and characterization of another LIM homeobox gene in Drosophila termed dlim1, a homolog of the vertebrate Lim-1 gene [10].
• Here we report that dLdb/Chip encodes a LIM-binding cofactor that controls Ap activity [22].
• Apterous-dependent expression of dLMO causes downregulation of Serrate and fringe and allows expression of delta in dorsal cells [23].

Analytical, diagnostic and therapeutic context of ap

• By Northern blot analysis, we demonstrate an increase in ap expression in pupae and adults as compared to embryos and larvae, suggesting that it is developmentally regulated [24].

References