Ambivalent partnership of the Drosophila posterior class Hox protein Abdominal-B with Extradenticle and Homothorax

PLoS Genet. 2025 Jan 13;21(1):e1011355. doi: 10.1371/journal.pgen.1011355. eCollection 2025 Jan.

Abstract

Hox proteins, a sub-group of the homeodomain (HD) transcription factor family, provide positional information for axial patterning in development and evolution. Hox protein functional specificity is reached, at least in part, through interactions with Pbc (Extradenticle (Exd) in Drosophila) and Meis/Prep (Homothorax (Hth) in Drosophila) proteins. Most of our current knowledge of Hox protein specificity stems from the study of anterior and central Hox proteins, identifying the molecular and structural bases for Hox/Pbc/Meis-Prep cooperative action. Posterior Hox class proteins, Abdominal-B (Abd-B) in Drosophila and Hox9-13 in vertebrates, have been comparatively less studied. They strongly diverge from anterior and central class Hox proteins, with a low degree of HD sequence conservation and the absence of a core canonical Pbc interaction motif. Here we explore how Abd-B function interface with that of Exd/Hth using several developmental contexts, studying mutual expression control, functional dependency and intrinsic protein requirements. Results identify cross-regulatory interactions setting relative expression and activity levels required for proper development. They also reveal organ-specific requirement and a binary functional interplay with Exd and Hth, either antagonistic, as previously reported, or synergistic. This highlights context specific use of Exd/Hth, and a similar context specific use of Abd-B intrinsic protein requirements.

MeSH terms

  • Animals
  • Body Patterning / genetics
  • Drosophila Proteins* / genetics
  • Drosophila Proteins* / metabolism
  • Drosophila melanogaster* / genetics
  • Drosophila melanogaster* / metabolism
  • Gene Expression Regulation, Developmental*
  • Homeodomain Proteins* / genetics
  • Homeodomain Proteins* / metabolism
  • Transcription Factors* / genetics
  • Transcription Factors* / metabolism

Substances

  • Drosophila Proteins
  • Homeodomain Proteins
  • hth protein, Drosophila
  • Abd-B proteins, Drosophila
  • exd protein, Drosophila
  • Transcription Factors

Grants and funding

Work in the laboratory of ESH was supported by grants BFU2017-86244-P and PID2020-113318GB-I00 from FEDER/Ministerio de Ciencia e Innovación-Agencia Estatal de Investigación-Consejo Superior de Investigaciones Científicas (https://www.aei.gob.es/). Work in the laboratory of YG was supported by the CNRS (Centre National de la Recherche Scientifique; https://www.cnrs.fr/fr) and AMU (Aix Marseille University https://www.univ-amu.fr/) and grants from AMIDEX n° ANR-11-IDEX-0001-02. Work in the laboratory of RK was supported by DBT-RLF grant by Department of Biotechnology, Government of India. Sanction No BT/RLF/Re-entry /22/20 13 (https://rcb.res.in). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.