Zebrafish mesonephric renin cells are functionally conserved and comprise two distinct morphological populations.
Zebrafish provide an excellent model in which to assess the role of the renin-angiotensin system in renal development, injury, and repair. In contrast to mammals, zebrafish kidney organogenesis terminates with the mesonephros. Despite this, the basic functional structure of the nephron is conserved across vertebrates. The relevance of teleosts for studies relating to the regulation of the renin-angiotensin system was established by assessing the phenotype and functional regulation of renin-expressing cells in zebrafish. Transgenic fluorescent reporters for renin (ren), smooth muscle actin (acta2), and platelet-derived growth factor receptor-beta (pdgfrb) were studied to determine the phenotype and secretory ultrastructure of perivascular renin-expressing cells. Whole kidneyrentranscription responded to altered salinity, pharmacological renin-angiotensin system inhibition, and renal injury. Mesonephricren-expressing cells occupied niches at the preglomerular arteries and afferent arterioles, forming intermittent epithelioid-like multicellular clusters exhibiting a granular secretory ultrastructure. In contrast, renin cells of the efferent arterioles were thin bodied and lacked secretory granules. Renin cells expressed the perivascular cell markersacta2andpdgfrbTranscriptional responses ofrento physiological challenge support the presence of a functional renin-angiotensin system and are consistent with the production of active renin. The reparative capability of the zebrafish kidney was harnessed to demonstrate thatrentranscription is a marker for renal injury and repair. Our studies demonstrate substantive conservation of renin regulation across vertebrates, and ultrastructural studies of renin cells reveal at least two distinct morphologies of mesonephric perivascularren-expressing cells.
University/British Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, Little France, The University of Edinburgh, Edinburgh, United Kingdom; srider@staffmail.ed.ac.uk.
Sebastien A
0000-0002-1020-4002
SA
Rider
Department of Physiology, Anatomy and Genetics, Oxford, United Kingdom; and.
Helen C
HC
Christian
University/British Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, Little France, The University of Edinburgh, Edinburgh, United Kingdom.
Linda J
LJ
Mullins
University/British Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, Little France, The University of Edinburgh, Edinburgh, United Kingdom.
Amelia R
AR
Howarth
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Calum A
CA
MacRae
University/British Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, Little France, The University of Edinburgh, Edinburgh, United Kingdom.
John J
JJ
Mullins
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D048430:Cell Shape; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D020286:Pericytes / Q000378:metabolism; D010641:Phenotype; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012083:Renin / Q000235:genetics / Q000378:metabolism*; D012084:Renin-Angiotensin System; D014158:Transcription, Genetic; D014928:Wolffian Ducts / Q000201:enzymology* / Q000648:ultrastructure; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D011993:Recombinant Fusion Proteins; D029961:Zebrafish Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D020797:Receptor, Platelet-Derived Growth Factor beta; D012083:Renin
kidney injury; perivascular; renin; renin-angiotensin system; zebrafish