Elsevier

Developmental Biology

Volume 382, Issue 2, 15 October 2013, Pages 555-566
Developmental Biology

Genomes and Developmental Control
A core transcriptional network composed of Pax2/8, Gata3 and Lim1 regulates key players of pro/mesonephros morphogenesis

https://doi.org/10.1016/j.ydbio.2013.07.028Get rights and content
Under an Elsevier user license
open archive

Highlights

  • A core regulatory subcircuit (Pax2/8, Gata3 and Lim1) locks the renal fate of the renal primordium.

  • It turns on a deeper layer of transcriptional regulators composed of Evi1, Idb4, Emx2 and Plac8.

  • These activate effector genes (Ret, Nephronectin, Wfdc2) with cellular and morphogenic activities.

Abstract

Translating the developmental program encoded in the genome into cellular and morphogenetic functions requires the deployment of elaborate gene regulatory networks (GRNs). GRNs are especially crucial at the onset of organ development where a few regulatory signals establish the different programs required for tissue organization. In the renal system primordium (the pro/mesonephros), important regulators have been identified but their hierarchical and regulatory organization is still elusive. Here, we have performed a detailed analysis of the GRN underlying mouse pro/mesonephros development. We find that a core regulatory subcircuit composed of Pax2/8, Gata3 and Lim1 turns on a deeper layer of transcriptional regulators while activating effector genes responsible for cell signaling and tissue organization. Among the genes directly affected by the core components are the key developmental molecules Nephronectin (Npnt) and Plac8. Hence, the pro/mesonephros GRN links together several essential genes regulating tissue morphogenesis. This renal GRN sheds new light on the disease group Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) in that gene mutations are expected to generate different phenotypic outcomes as a consequence of regulatory network deficiencies rather than threshold effects from single genes.

Abbreviations

CND
common nephric duct
CAKUT
congenital anomalies of the kidney and urinary tract
GDNF
glial cell line-derived neurotrophic factor
ChIP
chromatin immunoprecipitation

Keywords

Kidney development
Transcription
Pax2
Gata3
Lim1
CAKUT

Cited by (0)