Control of tissue morphogenesis by the HOX gene Ultrabithorax

Abstract

Mutations in the Ultrabithorax (Ubx) gene cause homeotic transformation of the normally two-winged Drosophila into a fourwinged mutant fly. Ubx encodes a HOX family transcription factor that specifies segment identity, including transformation of the second set of wings into rudimentary halteres. Ubx is known to control the expression of many genes that regulate tissue growth and patterning, but how it regulates tissue morphogenesis to reshape the wing into a haltere is still unclear. Here, we show that Ubx acts by repressing the expression of two genes in the haltere, Stubble and Notopleural, both of which encode transmembrane proteases that remodel the apical extracellular matrix to promote wing morphogenesis. In addition, Ubx induces expression of the Tissue inhibitor of metalloproteases in the haltere, which prevents the basal extracellular matrix remodelling necessary for wing morphogenesis. Our results provide a long-awaited explanation for how Ubx controls morphogenetic transformation.

Form and function of the apical extracellular matrix: new insights from Caenorhabditis elegans, Drosophila melanogaster, and the vertebrate inner ear

“…Evolutionary changes in appendage morphology may also reflect changes in aECM function: modern-day two-winged flies evolved from four-winged ancestors, with the vestigial posterior wings now functioning as balancing organs (halteres). The HOX transcription factor Ultrabithorax (Ubx) represses wing development and promotes haltere development, in part by repression of the aECM proteases Sb and Np, resulting in failure to degrade Dp and thereby preventing aECM remodeling and wing extension 28 . Development of another morphological novelty, the posterior lobe of D. melanogaster male genitalia, is also regulated by expanded expression of the aECM component Dp, revealing variation in aECM expression as a pathway of morphogenetic evolution 57 .…”

Ultrabithorax Is a Micromanager of Hindwing Identity in Butterflies and Moths

“…It would be challenging but providential to study Ubx expression and function in insect lineages with alternative wing sets such as Strepsiptera (T2 halteres, T3 wings), or in basal winged insects such as dragonflies and mayflies. At the molecular level, a characterization of the regulation, transcriptional targets, and chromatin-level interactions of Ubx is underway in a variety of systems (McKay and Lieb, 2013;Prasad et al, 2016;Sánchez-Higueras et al, 2019;Diaz-de-la-Loza et al, 2020), and we expect similar approaches in lepidopterans to yield valuable insights on the evolutionary specialization of serial homologs.…”

Characterisation of the role and regulation ofUltrabithoraxin sculpting fine-scale leg morphology

“…Ultrabithorax (Ubx) is expressed during embryogenesis and specifies the identity of thoracic and abdominal segments in Drosophila (Akam and Martinez-Arias, 1985;Castelli-Gair and Akam, 1995;Wilcox, 1984, 1985). Classically, this Hox gene represses wing identity and promotes haltere formation on the third thoracic (T3) segment through the direct regulation of potentially hundreds of genes (Bender et al, 1983;Diaz-de-la-Loza et al, 2020;Pavlopoulos and Akam, 2011;Tomoyasu, 2017;Weatherbee et al, 1998;Wilcox, 1984, 1985;White and Akam, 1985). Ubx also distinguishes the size and morphology of halteres at a more finescale level, in part through the autoregulation of differences in the expression levels between proximal and distal cells (Delker et al, 2019;Roch and Akam, 2000).…”