ZFIN ID: ZDB-PUB-190605-5
Tfap2a is a novel gatekeeper of nephron differentiation during kidney development
Chambers, B.E., Gerlach, G.F., Clark, E.G., Chen, K.H., Levesque, A.E., Leshchiner, I., Goessling, W., Wingert, R.A.
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
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.