The dachsous/fat/four-jointed signalling coordinates the uniform orientation of planar cell alignement in the drosophila abdominal epithelium

• Autores: Federica Mantione
• Directores de la Tesis: Enrique Martín Blanco (dir. tes.), Pedro Martínez Serra (tut. tes.)
• Lectura: En la Universitat de Barcelona ( España ) en 2016
• Idioma: inglés
• Tribunal Calificador de la Tesis: Marco Milán Kalbfleisch (presid.), Emilio Salo Boix (secret.), Marek Mlodzik (voc.)
• Programa de doctorado: Programa de Doctorado en Genética por la Universidad de Barcelona
• Materias:
  • Ciencias de la vida
    • Biología animal (zoología)
• Enlaces
  • Tesis en acceso abierto en: TESEO
• Resumen

  • Within multicellular organism, mature tissues and organs reach high degrees of order in the arrangement of their constituent cells. During morphogenesis the emergence of long-range order is subjected to multiple and multilevel developmental constrains. Complex series of temporal and spatial instructions must be integrated to account for reproducible and stereotyped mature tissue arrangements. A remarkable example is given by mature epithelial monolayers were cells are ringed together in specific morphologies via cell-cell adhesion and show highly organized planar patterns. Cells in epithelial tissues acquire a precise planar geometry that is often, if not always, evenly aligned with the tissue axes. Little is still known on the cellular mechanisms governing the axial orientation of cell arrangement and planar polarity. The research presented in this Thesis addressed these issues through the analysis of the developing abdominal epithelium of Drosophila melanogaster. We found that the abdominal epithelial cells reach their final arrangement within about 2 days of pupation. During this time, the abdominal epithelial tissue undergoes extensive morphogenesis by tissue expansion and cellular remodelling. During expansion, epithelial cells divide randomly relative to the tissue axis while migrating dorsally, while during remodelling cell adjust their final position within the plane of the epithelium while migrating anteriorly. When cell movements arrest, a stable arrangement of the cells within the plane of the segmental field is attained. At this time, epithelial cells are oriented and aligned among each other and throughout the tissues invariably in parallel to the A/P axis. We indicated as uniform orientation of planar cell alignment (PCA). We found that the axis orientation of PCA is evolving in a spatiotemporal precise manner along the A/P axis, and that this dynamic oriented behaviour was progressively modulated through expansion and remodelling. We found that the Dachsous/Fat/Four-jointed planar polarity pathway was specifically involved in the orientation of PCA. The steps followed to reach the axial orientation of PCA over developmental times correlates with the pattern of expression of the Dachsous/Fat/Four- jointed pathway. Such correlation was sustained by genetic interferences with the pathway components. We found that both the dynamics of the axis orientation of PCA and the attainment of its uniformity along the A/P axis were disrupted rearrangements in dachsous, fat or four-jointed mutants. We further found that loss of the axial uniform orientation of PCA in these mutants is accompanied by an overall reduction in mutual cell alignment and in cell shape elongation. These effects were also sustained through local interference in the activity of the pathway through clonal analyses. Local changes in pathway components induce the mutant clones to minimize cell-cell contacts with surrounding wild-type cells, suggesting differential adhesive properties between dachsous, fat, four-jointed mutant cells and the rest of the tissue. Surprisingly, we found that this effect was also directional and that Dachsous has an instructive role in driving the axis orientation of PCA, possibly by regulating the Fat localization across the cells/tissue. Therefore, from these findings, we propose that the Dachsous/Fat/Four-jointed pathway guide the orientation of PCA by favouring oriented cell-cell contact adhesiveness between abdominal epithelial cells. In particular, different adhesive properties imposed throughout the cell perimeter by Ds-Ft heterodimeric interaction at opposite edges of the cell might align epithelial cells changing and orienting their shape. Over time this biased interaction responding to the Dachsous gradient would be reinforced in response to the activity of Dachsous and Four-jointed onto Fat.