[en] 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.

[es] En los organismos multicelulares, tejidos y órganos tienen una disposición altamente organizada de las células que los constituyen. En particular, los tejidos epiteliales están constituidos por células que se disponen de manera ordenada con respecto a los ejes del cuerpo aunque los mecanismos que gobiernan esta disposición ordenada son poco conocidos. En esta tesis nos hemos focalizado en el estudio de los mecanismos que guían la orientación del eje celular en el plano de un epitelio en crecimiento. El epitelio abdominal de Drosophila constituye un sistema modelo para estudiar in vivo las dinámicas celulares que ocurren a lo largo de la morfogénesis tisular. Nuestros resultados demuestran que las células del epitelio abdominal empiezan a orientarse progresivamente llegando a una disposición espacial altamente ordenada. En esta disposición las células demuestran una preferencia en alinearse con el eje anteroposterior del tejido dando lugar a una orientación uniforme del alineamiento celular. Por otro lado, hemos descubierto que la vía de señalización de Dachsous/Fat/Four-jointed está involucrada en guiar el eje de orientación celular con respecto a el eje anteroposterior. Nuestros datos indican que los patrones de expresión de los genes dachsous, fat y four-jointed juegan un papel clave para el correcto alineamiento celular con el eje anteroposterior. De hecho, mutaciones en estos genes alteran el alineamiento espacial y afectan la elongación celular. Además, alteraciones locales en la actividad de cada uno de estos genes indican que están involucrados en la modulación orientada de los contactos adhesivos entre células vecinas. En resumen, estos resultados sugieren que la vía de señalización de Dachsous/Fat/Four- jointed tiene un papel clave en el alcance de una orientación celular uniforme a lo largo del tejido abdominal y, posiblemente, en otros epitelios.