Feedback control of organ size precision is mediated by BMP2-regulated apoptosis in the Drosophila eye

PLoS Biol. 2024 Jan 30;22(1):e3002450. doi: 10.1371/journal.pbio.3002450. eCollection 2024 Jan.

Abstract

Biological processes are intrinsically noisy, and yet, the result of development-like the species-specific size and shape of organs-is usually remarkably precise. This precision suggests the existence of mechanisms of feedback control that ensure that deviations from a target size are minimized. Still, we have very limited understanding of how these mechanisms operate. Here, we investigate the problem of organ size precision using the Drosophila eye. The size of the adult eye depends on the rates at which eye progenitor cells grow and differentiate. We first find that the progenitor net growth rate results from the balance between their proliferation and apoptosis, with this latter contributing to determining both final eye size and its variability. In turn, apoptosis of progenitor cells is hampered by Dpp, a BMP2/4 signaling molecule transiently produced by early differentiating retinal cells. Our genetic and computational experiments show how the status of retinal differentiation is communicated to progenitors through the differentiation-dependent production of Dpp, which, by adjusting the rate of apoptosis, exerts a feedback control over the net growth of progenitors to reduce final eye size variability.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Drosophila Proteins* / genetics
  • Drosophila melanogaster
  • Drosophila* / genetics
  • Eye
  • Feedback
  • Organ Size
  • Retina

Substances

  • Drosophila Proteins

Grants and funding

PID2019-109320GB-100 to SA and JM-G; PID2022-142185NB-C21 to SA; PID2022-142185NB-C22 to JM-G; PGC2018-093704-B-I00 and PID2021-122671NB-I00 to FC. Agencia Estatal de Investigacion, SPAIN: https://www.aei.gob.es/ The CABD and CNB also received funding from the Spanish Agencia Estatal de Investigacion through the “Maria de Maeztu” and “Severo Ochoa” Centres of Excellence Program through grants CEX2020-001088-M and SEV 2017-0712, respectively, from Agencia Estatal de Investigación, SPAIN: https://www.aei.gob.es/. We acknowledge support from the Scientific Network LifeHub. CSIC funded by the Consejo Superior de Investigaciones Científicas (CSIC), SPAIN: https://www.csic.es/en. FCT (Fundaçao para a Ciencia e a Tecnologia, Portugal). Grant number: EXPL/BIA-BID/0267/2021) to PSP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.