Gines Morata

..Recent work in other organisms suggests that paracrine signaling from apoptotic cells may be of general significance in wound healing and tissue regeneration in metazoans...

..In a recent issue of Cell, Li and Baker (2007) show in the Drosophila wing disc that cells fated to die induce in neighboring cells the activity of engulfment genes, whose function is essential to complete the apoptotic program...

..How do Drosophila appendages develop, what gives each appendage its unique identity, and what can the fruit fly teach us about appendage development in vertebrates?..

..We have also identified the gene teashirt (tsh) as a positive regulator of hth in the hinge. tsh plays a role specifying hinge structures, possibly in co-operation with hth...

..We speculate that, although the basic mechanisms are similar, there are significant differences in the manner the body trunk and appendages respond to them...

..We propose that this property is a reflection of the initial function of the btd/Sp1 genes that consists of establishing the fate of the ventral disc primordia and determining their pattern and growth...

..We also present evidence for a molecular interaction between the Hth and the Eyg proteins that may be important for the patterning of the alpha subdomain...

..The activity of eyg gives rise to a new notum subdivision that acts upon the pre-extant one generated by the Iro genes and pnr. As a result the notum becomes subdivided into four distinct genetic domains...

..We argue that pnr acts like a classical selector gene but differs in that its expression is not propagated through cell divisions...

..In the absence of the Hh pathway, cad induces internal analia development, probably by activating the brachyenteron and even-skipped genes...

..These results, together with prior work on its function in adults, suggest that pnr is a major factor in the genetic subdivision of the body of Drosophila...

..As the Hoxd10 gene has the same properties as Drosophila BX-C genes, we suggest that the control mechanism of subcellular distribution of Exd found in Drosophila probably operates in other organisms as well...

....

..Comparison between Drosophila and other species suggests a common functional organization of homeotic complexes in the animal kingdom...

..Our findings indicate that exd is critically involved in adult morphogenesis, not only in the homeotic function but also in several other developmental processes...

..The formation of a tumor requires in addition the formation of a microenvironment that allows mutant cells to evade cell competition...

..We propose that hth/exd function contributes to the normal identity of proximal cells both by limiting the influence of the Dpp and Wg pathways and by activating proximal genes like teashirt (tsh) and aristaless (al)...

..Thus there may be a common prepattern for the entire structure...

..We propose that this mechanism does not act by preventing cell divisions, but by lengthening the division cycle...

....

..However, unlike other homeotic genes, Dll expression and function is not defined by a cell lineage border. Dll also performs a secondary and late function required for the normal patterning of the wing...

..The values predicted by the simulation are very close to those obtained experimentally...

..We suggest that a similar process of uncoupling apoptosis initiation and cell death may occur during tumour formation in mammalian cells...

..Brk appears to downregulate the activity of genes that control cell proliferation, such as bantam...

..In compartments containing undead cells, the adventitious Dpp/Wg signalling results in hyperplastic overgrowths...

..We describe their effects in epithelial architecture and growth in some detail, and discuss the possible relationship between undead cells and compensatory proliferation...

..Our results also indicate that most or all the larval head structures derive from precursor cells of ventral origin...

..Our results also suggest that the differentiation of cirri is induced by Dfd-expressing cells in non-expressing neighboring cells, and that this interaction occurs across the parasegmental border...

..Finally, we show that in the crustacean Artemia, exd and Dll are expressed in comparable patterns as in Drosophila, suggesting a conserved genetic mechanism subdividing the arthropod limb...

..In segment A9 the highly expressed Ubx product is phenotypically suppressed by the r product of Abdominal-B. The presence of high levels of Ubx protein is also irrelevant in the telson...

..We have established a hierarchical order among these genes: Antp less than Scr less than Ubx less than abd-A less than Abd-B. In addition, we show that the engrailed gene is ectopically active in Pc- imaginal cells...

..Hence our results challenge the view that these, and possibly other cross-regulatory interactions have a role in determining segmental identity...

..We argue that the different Ubx proteins are developmentally equivalent and that the slight mutant phenotype observed in UbxMX17 flies is not due to the abnormal set of Ubx proteins but to a breakpoint in a cis-regulatory region...

..It is repressed by the BX-C genes in the meso-, metathoracic and the abdominal segments...

..Finally, we show that the abd-A gene is down-regulated in part of the Abdominal-B (Abd-B) domain, precisely in those regions where the Abd-B gene is expressed at high levels...

..We suggest that restriction of Meis1/Hth to proximal regions of the vertebrate and insect limb is essential to specify cell fates and differentiation patterns along the P-D axis of the limb...

..The boundary between two of these domains coincides with localized expression of the signaling molecule wingless...

..Regulatory region 1, 3' to the transcription unit, contains positive and negative regulatory elements. Regulatory region 2, 5' to the transcription unit, establishes the correct level of abd-A activity in the abdominal metameres...

..We speculate that the region altered in the mutations may have a wildtype function to ensure cis-autonomy of the regulation of Ubx transcription...