Details

Autor(en) / Beteiligte

• Chambers, Brooke E
• Clark, Eleanor G
• Gatz, Allison E
• Wingert, Rebecca A

Titel

Kctd15 regulates nephron segment development by repressing Tfap2a activity

Ist Teil von

• Development (Cambridge), 2020-12, Vol.147 (23)

Ort / Verlag

England: The Company of Biologists Ltd

Erscheinungsjahr

2020

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• A functional vertebrate kidney relies on structural units called nephrons, which are epithelial tubules with a sequence of segments each expressing a distinct repertoire of solute transporters. The transcriptiona`l codes driving regional specification, solute transporter program activation and terminal differentiation of segment populations remain poorly understood. Here, we demonstrate that the KCTD15 paralogs and function in concert to restrict distal early (DE)/thick ascending limb (TAL) segment lineage assignment in the developing zebrafish pronephros by repressing Tfap2a activity. During renal ontogeny, expression of these factors colocalized with in distal tubule precursors. loss primed nephron cells to adopt distal fates by driving , and expression. These phenotypes were the result of Tfap2a hyperactivity, where -deficient embryos exhibited increased abundance of this transcription factor. Interestingly, reciprocally promoted and transcription, unveiling a circuit of autoregulation operating in nephron progenitors. Concomitant knockdown with overexpression further expanded the DE population. Our study reveals that a transcription factor-repressor feedback module employs tight regulation of Tfap2a and Kctd15 kinetics to control nephron segment fate choice and differentiation during kidney development.