Morphogenesis is consequence of lots of small coordinated variations that occur during development. In proliferating stages, tissue growth is coupled to changes in shape and organization. A number of studies have analyzed the topological properties of proliferating epithelia using the Drosophila wing disc as a model. These works are based in the existence of a fixed distribution of these epithelial cells according to their number of sides. Cell division, cell rearrangements or a combination of both mechanisms have been proposed to be responsible for this polygonal assembling. Here, we have used different system biology methods to compare images from two close proliferative stages that present high morphological similarity. This approach enables us to search for traces of epithelial organization. First, we show that geometrical and network characteristics of individual cells are mainly dependent on their number of sides. Second, we find a significant divergence between the distribution of polygons in epithelia from mid-third instar larva versus early prepupa. We show that this alteration propagates into changes in epithelial organization. Remarkably, only the variation in polygon distribution driven by morphogenesis leads to progression in epithelial organization. In addition, we identify the relevant features that characterize these rearrangements. Our results reveal signs of epithelial homogenization during the growing phase, before the planar cell polarity pathway leads to the hexagonal packing of the epithelium during pupal stages.
References
[1]
Lecuit T, Le Goff L (2007) Orchestrating size and shape during morphogenesis. Nature 450: 189–192.
[2]
Axelrod JD (2006) Cell shape in proliferating epithelia: a multifaceted problem. Cell 126: 643–645.
[3]
Escudero LM, Bischoff M, Freeman M (2007) Myosin II regulates complex cellular arrangement and epithelial architecture in Drosophila. Dev Cell 13: 717–729.
[4]
Bertet C, Sulak L, Lecuit T (2004) Myosin-dependent junction remodelling controls planar cell intercalation and axis elongation. Nature 429: 667–671.
[5]
Simoes Sde M, Blankenship JT, Weitz O, Farrell DL, Tamada M, et al. (2010) Rho-kinase directs Bazooka/Par-3 planar polarity during Drosophila axis elongation. Dev Cell 19: 377–388.
[6]
Leptin M, Grunewald B (1990) Cell shape changes during gastrulation in Drosophila. Development 110: 73–84.
[7]
Costa M, Wilson ET, Wieschaus E (1994) A putative cell signal encoded by the folded gastrulation gene coordinates cell shape changes during Drosophila gastrulation. Cell 76: 1075–1089.
[8]
Parks S, Wieschaus E (1991) The Drosophila gastrulation gene concertina encodes a G alpha-like protein. Cell 64: 447–458.
[9]
Kolsch V, Seher T, Fernandez-Ballester GJ, Serrano L, Leptin M (2007) Control of Drosophila gastrulation by apical localization of adherens junctions and RhoGEF2. Science 315: 384–386.
[10]
Barrett K, Leptin M, Settleman J (1997) The Rho GTPase and a putative RhoGEF mediate a signaling pathway for the cell shape changes in Drosophila gastrulation. Cell 91: 905–915.
[11]
Pilot F, Lecuit T (2005) Compartmentalized morphogenesis in epithelia: from cell to tissue shape. Dev Dyn 232: 685–694.
[12]
Haigo SL, Hildebrand JD, Harland RM, Wallingford JB (2003) Shroom induces apical constriction and is required for hingepoint formation during neural tube closure. Curr Biol 13: 2125–2137.
[13]
Hildebrand JD, Soriano P (1999) Shroom, a PDZ domain-containing actin-binding protein, is required for neural tube morphogenesis in mice. Cell 99: 485–497.
[14]
Milan M, Campuzano S, Garcia-Bellido A (1996) Cell cycling and patterned cell proliferation in the Drosophila wing during metamorphosis. Proc Natl Acad Sci U S A 93: 11687–11692.
[15]
Martin FA, Herrera SC, Morata G (2009) Cell competition, growth and size control in the Drosophila wing imaginal disc. Development 136: 3747–3756.
[16]
Farhadifar R, Roper JC, Aigouy B, Eaton S, Julicher F (2007) The influence of cell mechanics, cell-cell interactions, and proliferation on epithelial packing. Curr Biol 17: 2095–2104.
[17]
Gibson MC, Patel AB, Nagpal R, Perrimon N (2006) The emergence of geometric order in proliferating metazoan epithelia. Nature 442: 1038–1041.
[18]
Gho M, Bellaiche Y, Schweisguth F (1999) Revisiting the Drosophila microchaete lineage: a novel intrinsically asymmetric cell division generates a glial cell. Development 126: 3573–3584.
[19]
Classen AK, Anderson KI, Marois E, Eaton S (2005) Hexagonal packing of Drosophila wing epithelial cells by the planar cell polarity pathway. Dev Cell 9: 805–817.
[20]
Martinez-Arias M, Stewart A (2002) Molecular Principles of Animal Development: OUP Oxford. 424 p.
[21]
Patel AB, Gibson WT, Gibson MC, Nagpal R (2009) Modeling and inferring cleavage patterns in proliferating epithelia. PLoS Comput Biol 5: e1000412.
[22]
Aegerter-Wilmsen T, Smith AC, Christen AJ, Aegerter CM, Hafen E, et al. (2010) Exploring the effects of mechanical feedback on epithelial topology. Development 137: 499–506.
[23]
Gibson WT, Gibson MC (2009) Cell topology, geometry, and morphogenesis in proliferating epithelia. Curr Top Dev Biol 89: 87–114.
[24]
Eaton S, Julicher F (2011) Cell flow and tissue polarity patterns. Curr Opin Genet Dev 21: 747–752.
[25]
Gibson WT, Veldhuis JH, Rubinstein B, Cartwright HN, Perrimon N, et al. (2011) Control of the mitotic cleavage plane by local epithelial topology. Cell 144: 427–438.
[26]
Escudero LM, Costa Lda F, Kicheva A, Briscoe J, Freeman M, et al. (2011) Epithelial organisation revealed by a network of cellular contacts. Nat Commun 2: 526.
[27]
Costa LD, Rodrigues FA, Travieso G, Boas PRV (2007) Characterization of complex networks: a survey of measurements. Advances in Physics 56: 167–242.
[28]
Sáez A, Rivas E, Montero-Sánchez A, Paradas C, Acha B, et al.. (2013) Quantifiable diagnosis of muscular dystrophies and neurogenic atrophies through network analysis. BMC Medicine 11..
[29]
Aldaz S, Escudero LM, Freeman M (2010) Live imaging of Drosophila imaginal disc development. Proc Natl Acad Sci U S A 107: 14217–14222.
[30]
Freeman LC (1979) Centrality in social networks: Conceptual clarification. Social Networks 1: 215–239.
[31]
Newman M (2005) A measure of betweeness centrality based on random walks. Social Networks 27: 39–54.
[32]
Aegerter-Wilmsen T, Heimlicher MB, Smith AC, de Reuille PB, Smith RS, et al. (2012) Integrating force-sensing and signaling pathways in a model for the regulation of wing imaginal disc size. Development 139: 3221–3231.
[33]
Fukunaga K (1990) Introduction to Statistical Pattern Recognition: Academic Press
[34]
Costa LD, Cesar RMJ (2000, 2009)Shape Analysis and Classification: Theory and Practice: CRC Press. 680 p.
