Poster Presentation Hunter Cell Biology Meeting 2025

Understanding the role of pericytes in controlling blood brain barrier maintenance using both zebrafish and mouse brain pericyte deficient models. (#219)

Alison Farley 1 2 3 4 , Oguzhan Baltaci 1 2 , Andrea UsseglioGaudi 1 2 , Stefanie Dudczig 1 2 , Maria Cristina Rondon Galeano 1 2 , Robert Parton 5 , Anne Lagendijk 5 , Ye-Wheen Lim 5 , James Rae 5 , Carolyn deGraaf 4 , Ben Hogan 1 2 3
  1. Organogenesis and Cancer Program, Peter MacCullum Cancer Centre, Melbourne, VIC, Australia
  2. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Vic 3000, Australia
  3. Department of Anatomy and Physiology, Univeristy of Melbourne, Melbourne, Vic 3000, Australia
  4. Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
  5. Institute for Molecular Bioscience, The University of Queensland , St Lucia , Queensland, Australia

The Neuro-vasculature plays a central role in the pathogenesis and treatment of diseases of the brain.  Central to the development and function of brain vasculature is the neurovascular unit (NVU). Within the NVU, specialised endothelial cells (ECs), pericytes and several neural cells form the blood brain barrier (BBB), that protects the brain from harmful metabolites present in the circulation. A central paradigm in BBB biology is whether the pericytes control BBB formation and function. It has been shown that mice with reduced pericytes (Pdgfbret/ret) have a compromised BBB due to increased endothelial transcytosis1. To understand the mechanistic detail of how pericytes control BBB function we developed a zebrafish mutant (pdgfrßuq30bh) that lacks brain pericytes and found that pericytes control the initial patterning of cerebral vasculature during embryonic development but these animals do not exhibit BBB impairment. Rather than a general increase in BBB permeability seen in the Pdgfbret/ret model, this vertebrate model of pericyte deficiency displays no BBB leakage until aneurysms formed followed by widespread cerebrovascular haemorrhage in adulthood2.  These finding led us to revisit the pericyte deficient Pdgfbret/ret mice and we found widespread cerebral haemorrhages during embryogenesis and disrupted vessel patterning. Taken together, detailed analysis of the zebrafish model of pericyte deficiency, and the Pdgfbret/ret mouse, suggest the primary role of pericytes is cerebrovascular patterning and vascular integrity but no evidence of the regulation of transcytosis. This work suggests that reported BBB defects in pericyte deficiency models is likely due to vessel rupture (micro-haemorrhage) and warrants further detailed analysis of the acute phenotypes seen upon pericyte depletion.

  1. Pericytes regulate the blood-brain barrier. Armulik et. al. Nature, 2010.
  2. Vascular mural cells protect the adult brain from haemorrhage but do not control the blood-brain barrier in developing zebrafish. Baltaci. et. al. eLife 2025.