Regulation of leg size and shape: Involvement of the Dachsous‐fat signaling pathway

Abstract

How limb size and shape is regulated is a long-standing question in developmental and regeneration biology. Recently, the protocadherin Dachsous-Fat (Ds-Ft) signaling pathway has been found to be essential for wing development of the fly and leg regeneration of the cricket. The Ds-Ft signaling pathway is linked to the Warts-Hippo (Wts-Hpo) signaling pathway, leading to cell proliferation. Several lines of evidence have suggested that the Wts-Hpo signaling pathway is involved in the control of organ size, and that this pathway is regulated by Ds-Ft and Merlin-Expanded, which are linked to morphogens such as decapentaplegic/bone morphogenic protein, Wingless/Wnt, and epidermal growth factor. Here we review recent progress in elucidating mechanisms controlling leg size and shape in insects and vertebrates, focusing on the Ds-Ft signaling pathway. We also introduce a working model, Ds-Ft steepness model, to explain how steepness of the Ds-Ft gradient controls leg size along the proximodistal axis. Developmental Dynamics 240:1028-1041,

Analysis of RNA-Seq data reveals involvement of JAK/STAT signalling during leg regeneration in the cricket Gryllus bimaculatus

“…The expression of apoptotic genes, MMPs, piwi and AGO3 was upregulated in RLs (supplementary material Table S2), similar to regeneration in other organisms (Chera et al, 2011;Li et al, 2011;Maki et al, 2010;Reddien et al, 2005 Table S4) and JAK/STAT (Table 1) were also upregulated in RLs (Agata and Inoue, 2012;Bando et al, 2011a;Bando et al, 2009;Bando et al, 2011b;Nakamura et al, 2008a;Nakamura et al, 2008b). Supplementary material Tables S5 and S6 list transcription and epigenetic factors, respectively, that were upregulated in RLs, which could be key factors for cell fate determination and reprogramming (Maki et al, 2010;McClure and Schubiger, 2008;Meissner, 2010;Onder et al, 2012;Rao et al, 2009;Repiso et al, 2011;Stewart et al, 2009).…”

An extended steepness model for leg-size determination based on Dachsous/Fat trans-dimer system

“…Since knock-down of the expression of Gryllus dachsous ( Gb′ds ) or Gb′fat ( Gb′ft ) resulted in shorter regenerated legs, they assumed that the Ds/Ft system was likely involved in determination of leg length. In contrast, when expressions of Gb′Merlin ( Gb′Mer ) and Gb′expanded ( Gb′ex ), which are upstream components of the Hippo pathway12, encoding the membrane-associated FERM-domain proteins were knocked down by RNAi during leg regeneration, the regenerated leg became longer than normal1113. To further analyze their data, they applied the Ds/Ft steepness model2, assuming a gradient of the Ds/Ft tarns-dimer was linear, as shown in Fig.…”

“…To further analyze their data, they applied the Ds/Ft steepness model2, assuming a gradient of the Ds/Ft tarns-dimer was linear, as shown in Fig. 1c13, since they did not know any protein distribution of Ds and Ft in the leg segment of the cricket. After amputation of the leg, regeneration started and regeneration (cell proliferation) stopped when the gradient of the Ds/Ft trans-dimers reached a threshold value ( diff ) that determined normal leg length11.…”

“…In the steepness model, there are 3 parameters, h : the initial height of the gradient, s : slope, and diff : threshold value that determines length. Bando et al 13. assumed that the h value became low in the case of the Ds/Ft RNAi experiment, in which the regenerated leg was short, while the diff value became low in the case of the ex/Mer RNAi experiment, in which the regenerated leg became longer.…”

“…In the case of the cricket leg, we assumed the presence of Ds/Ft trans-homodimer gradients, based on their expression patterns in the leg bud13. In the cricket leg bud, expression of the Gb′ds was intense in the distal region of each leg segment and showed a negative gradient to the distal direction, while that of Gb′ft was opposite, i.e., intense in the proximal region and show a negative gradient to the distal direction, which did not appear linear (although we could not observe any protein distribution).…”