Regulation of BMP activity and range in Drosophila wing development

Abstract

Bone morphogenetic protein (BMP) signaling controls development and maintenance of many tissues. Genetic and quantitative approaches in Drosophila reveal that ligand isoforms show distinct function in wing development. Spatiotemporal control of BMP patterning depends on a network of extracellular proteins Pent, Ltl and Dally that regulate BMP signaling strength and morphogen range. BMP-mediated feedback regulation of Pent, Ltl, and Dally expression provides a system where cells actively respond to, and modify, the extracellular morphogen landscape to form a gradient that exhibits remarkable properties, including proportional scaling of BMP patterning with tissue size and the modulation of uniform tissue growth. This system provides valuable insights into mechanisms that mitigate the influence of variability to regulate cell-cell interactions and maintain organ function.

Precision Optogenetic Tool for Selective Single- and Multiple-Cell Ablation in a Live Animal Model System

“…For example, the adult wings develop from wing imaginal discs. During larval development, the bone morphogenetic protein homolog decapentaplegic (dpp) is expressed in a narrow band of cells anterior to the anteroposterior (A/P) compartment boundary (Figure 4B) (Raftery and Umulis, 2012). The dpp-expressing cells in the wing blade primordium contribute to tissues anterior to the A/P boundary in the adult wing blade (Figure 4C).…”

“…In the adult, the wing that was developed from the illuminated wing imaginal disc indicated obvious loss of cells (Figures 4D, 4E, and S4). The cells between longitudinal veins 3 and 4 appeared to be lost; these cells are known to be descendant from the dpp-expressing cells in the wing blade primordium (Figure 4C) (Raftery and Umulis, 2012). On the other hand, the tissues developed from the dpp-non-expressing cells seemed normal including the longitudinal veins 1, 2, and 5, and the posterior cross vein.…”

Smad1 stabilization and delocalization in response to the blockade of BMP activity

“…They play critical roles in many cellular processes and in tissue homeostasis and development [6,7]. BMPs form a morphogen gradient that controls the dorsal-ventral patterning of invertebrate and vertebrate embryos [8,9]. Mouse genetic studies confirmed the essential roles for BMP-Smad1/5/8 signaling in early embryonic development and postnatal tissue homeostasis [7].…”

“…BMPs form a morphogen gradient that decides cell fates during early embryonic development [8,9,43]. In addition, BMP-Smad1 signaling controls many other aspects of development and tissue homeostasis and its dysregulation leads to the development of a number of diseases, including cancer and skeletal and vascular diseases.…”

Fine-tuned shuttles for bone morphogenetic proteins

“…Of particular interest in the wing primordium are the GPI-linked Drosophila glypicans, Dally and Dally-like protein (Dlp), and two secreted molecules, Pentagone (Pent) and Larval Translucida (Ltl) that appear to provide a ‘BMP shuttle’ function while ensuring tight feedback controls (reviewed in [84]) (Figure 4). The ability of Dally to stabilize Dpp at the cell surface in trans , has led to a model by which BMPs are handed off from one cell to another in a series of glypican-BMP association-dissociations [85]**.…”