PUBLICATION

Tfap2a is a novel gatekeeper of nephron differentiation during kidney development

Authors
Chambers, B.E., Gerlach, G.F., Clark, E.G., Chen, K.H., Levesque, A.E., Leshchiner, I., Goessling, W., Wingert, R.A.
ID
ZDB-PUB-190605-5
Date
2019
Source
Development (Cambridge, England)   146(13): (Journal)
Registered Authors
Chambers, Brooke, Chen, Karen, Gerlach, Gary F., Goessling, Wolfram, Levesque, Anna, Wingert, Rebecca
Keywords
Differentiation, Kidney, Nephron, Segmentation, Zebrafish, irx1a, irx3b, tfap2a, tfap2b
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Body Patterning/genetics
  • Cell Differentiation/genetics
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental
  • Genes, Switch/physiology
  • Kidney/embryology*
  • Kidney/metabolism
  • Nephrons/embryology*
  • Nephrons/metabolism
  • Organogenesis/genetics*
  • Pronephros/embryology
  • Pronephros/growth & development
  • Pronephros/metabolism
  • Transcription Factor AP-2/genetics
  • Transcription Factor AP-2/physiology*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
PubMed
31160420 Full text @ Development
Abstract
Renal functional units known as nephrons undergo patterning events during development that create a segmental array of cellular compartments with discrete physiological identities. Here, from a forward genetic screen using zebrafish we report the discovery that transcription factor AP-2 alpha (tfap2a) coordinates a gene regulatory network that activates the terminal differentiation program of distal segments in the pronephros. We found that tfap2a acts downstream of Iroquois homeobox 3b (irx3b), a distal lineage transcription factor, to operate a circuit consisting of tfap2b, irx1a, and genes encoding solute transporters that dictate the specialized metabolic functions of distal nephron segments. Interestingly, this regulatory node is distinct from other checkpoints of differentiation like polarity establishment and ciliogenesis. Thus, our studies reveal insights into the genetic control of differentiation, where tfap2a is essential to regulate a suite of segment transporter traits at the final tier of zebrafish pronephros ontogeny. These findings have relevance for understanding renal birth defects, as well as efforts to recapitulate nephrogenesis in vivo to facilitate drug discovery and regenerative therapies.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes