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Gene name - lozenge Synonyms - Cytological map position - 8D8-9 Function - transcription factor Keywords - eye, peripheral nervous system |
Symbol - lz FlyBase ID:FBgn0002576 Genetic map position - 1-27.7 Classification - AML-1 homolog Cellular location - nuclear |
EvoprintHD of Lozenge
In Drosophila, the lozenge gene complex is considered a historically classic loci. It was the first genetic locus to reveal a genetic fine structure, more than a decade before the elegant genetic fine structure analysis of the rII locus in bacteriophage T4 (Green, 1990 and references). Work with lozenge proved that genes could be subdivided into constituent parts, much like atoms can be broken down into more fundamental particles. The occurrence of interallelic recombination allowed the mapping of lozenge alleles to one of four discrete sub-loci: spectacle, krivshenko, lozenge and glossy. With the recent cloning of lozenge, the genetic basis of these sub-loci can now be analyzed.
The involvement of lozenge in the development of the antennal olfactory sense organs is of particular interest both because it is a relatively neglected area of research and because the olfactory sense organs do not show a stereotyped arrangement or fixed cellular composition characteristic of cells of the external sense organs (See Peripheral nervous system). The fixed pattern of external sense organs is found for taste (gustatory) sensilla, located on the labellum, pharynx, leg, wing and female genitalia. Olfactory sensilla are found only on the antenna (Stocker, 1994). In the PNS, all the cells comprising a sensory element are derived from a single progenitor cell (the sensory mother cell). In contrast, cells of the olfactory sensilla (found only in antenna) are not related to a common progenitor by lineage (Ray, 1995).
There are three morphologically distinct types of olfactory sensilla arranged in broad zones on the surface of the third (terminal) antennal segment. There appears to be no strict control of the spacing between neighboring sensilla. Moving from medial to lateral, the three types are: basiconical sensilla, coeloconic sensilla and tricoid sensilla. Olfactory and taste sensilla share a common anatomical design: each consists of a cuticular shaft (hair cell or trichogen), a socket (outermost cell or tormogen), and a sheath cell (glial) that wraps around the multiple neurons of each sensillum. All the sensory neurons from the third antennal segment project to the olfactory lobe in the brain. The cephalic disc (eye-antennal disc) forms the whole of the head capsule in the adult. An "enhancer trap" line A101 is used as a marker of sensillum development, as the reporter enzyme ß-galactosidase is expressed specifically in the sensory progenitors and subsequently in all cells of a developing sensillum. In addition, a monoclonal antibody 22C10 (see Futsch) recognizes all developing and adult neurons and also the sensory progenitors.
There are two waves of sensillogenesis in antenna, as indicated by the appearance of ß-gal-positive cells: one takes place at 0-10 hr after puparium formation, and a second at 16-18 hr after puparium formation. Precursors specified during the first wave are uniformly spread over the cephalic disc, and precursors arising in the later time interval are interspersed between the earlier, more mature, sensilla. Each wave does not specify a single type of sense organ, but each of the three types is specified in both waves. Between 130 and 140 precursors express ß-gal in the early wave, and these precursors are termed sensillum "founder cells" (FCs). FCs give rise to the cellular constituents (neural, glial and support) of each sensillium.
During 10- to 16-hr after puparium formation, the number of FCs decreases, to be replaced by groups of two to four cells. These groups are referred to as presensillum clusters (PFCs) since the cells in each such cluster have been found to form a single sensillum. The nuclei of the cells in each group are all equivalent in size and smaller than those of the FCs observed in earlier discs. It is thought that FCs, in spite of their larger nuclei, do not undergo division during the formation of PFCs since no mitotic figures are present. Because of the absence of DNA synthesis and mitotic figures, it is believed that additional cells of the cluster (other than FCs) are recruited from surrounding cells, and not derived from FCs by descent. By 14 hours, one or two cells of each PSC can be stained with MAB22C10. These cells have basally placed nuclei. Cells with basal nuclei are the progenitors of the sensory neurons in each PSC. Since there is no DNA synthesis in the cells on the surface of the antenna during this period, it is concluded that olfactory sense organ progenitors do not replicate DNA before the PSC formation.
Subsequently, between 16 and 17 hours, cells of each PSC undergo mitosis before terminal differentiation, but cells of the PSC divide only once before they undergo terminal differentiation. This means that pairs of cells within each sensillum are "sisters." Three cells among these sisters locate apically to form the support cells; the cell bodies of neuronal cells locate basally. By 18 hours, axons can be seen leaving the PSCs. From one to four neurons innnervate each sensillium. Therefore the total number of cells in a single sensory cluster varies from four to seven, at least one neuron and three support cells (Ray, 1995).
In lozenge mutants, all basiconic sensilla and some of the trichoid sensilla are lacking. MAb22C10 positive precursors of the basiconic sensilla fail to develop. In lz mutants examined at 10 hours, there is a reduction of PSCs to approximately 60, versus 132 in wild type. While a lack of sensilla is apparent all over the antennal surface by 26 hours, it is more pronounced in the region normally occupied by the big basiconic sensilla. This implicates lozenge in the process of determination of founder cells of basiconic sensilla (Ray, 1995).
In eye morphogenesis lozenge is required to specify the R7 equivalence group. lozenge is active in R7 and cone cells, where it functions to silence seven-up. lozenge is silent in R3/R4, allowing for the expression of seven-up, and the specification of R3/R4 cell fates. Lozenge plays a dual rule in R1/R6 cells. As seven-up is required to specify R1/R6 fate, Lozenge cannot act to completely silence seven-up function, but apparently acts to reduce seven-up activity. At the same time, Lozenge activates Bar gene expression in the R1/R6 pair, an essential function required for specification of the fate of that pair. It will be of great interest to discover how lozenge is regulated, as it appears to have a critical role in specification of alternative neural fates (Daga, 1996).
Exons - 6
The central domain of Lozenge contains a region homologous to AML1 (acute myeloid leukemia 1). This region includes the dimerization and DNA binding domain, as well as a putative ATP-binding site that is completely conserved among proteins of this group. There is a region of conserved amino acids of unknown function (VWRPY) at the C-terminus. In the homologous domain, LZ sequence has 71% identity to AML1 and 69% homology to Runt. The LZ sequence also possesses an alanine-rich stretch and a glutamine-rich region in the C-terminal portion of the molecule (Daga, 1996).
date revised: 5 MAR 97
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