title: Zebrafish nephrogenesis involves dynamic spatiotemporal expression changes in renal progenitors and essential signals from retinoic acid and irx3b.
abstract: Kidney nephrons are composed of proximal and distal tubule segments that perform unique roles in excretion. The developmental pathways that establish nephron segment identities from renal progenitors are poorly understood. Here, we used the zebrafish pronephros to study nephron segmentation. We found that zebrafish nephron progenitors undergo elaborate spatiotemporal expression changes of many genes before adopting a segment fate. Initially, two domains of nephron progenitors are established, then are subdivided and demarcate individual nephron segments. Using genetic and chemical genetic models of retinoic acid (RA) deficiency, we discovered that RA modulates rostral progenitor formation. To delineate downstream pathways, we knocked down the irx3b transcription factor and found it regulates proximal tubule segment size and distal segment differentiation. Our results suggest a model whereby RA patterns the early field of nephron progenitors, with subsequent factors like irx3b acting to refine later progenitor subdomains and ensure activation of segment-specific gene programs.
authors.affiliation: Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Wingert
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Davidson
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology / Q000502:physiology; D009399:Nephrons / Q000166:cytology / Q000196:embryology*; D038081:Organogenesis / Q000502:physiology*; D060910:Pronephros / Q000166:cytology / Q000196:embryology*; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism*; D015027:Zebrafish / Q000033:anatomy & histology / Q000196:embryology / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C568409:irx3b protein, Danio rerio; D014212:Tretinoin