BMP signaling in the nephron progenitor niche
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Leif Oxburgh & Aaron C. Brown & Jennifer Fetting & Beth Hill
- چاپ و سال / کشور: 2011
Description
Bone morphogenic proteins (BMPs) play diverse roles in embryonic kidney development, regulating essential aspects of both ureteric bud and nephron development. In this review, we provide an overview of reported expression patterns and functions of BMP signaling components within the nephrogenic zone or nephron progenitor niche of the developing kidney. Reported in situ hybridization results are relatively challenging to interpret and sometimes conflicting. Comparing these with high-resolution microarray gene expression data available in Gudmap, we propose a consensus gene expression pattern indicating that essential components of both the Smad-mediated pathway and the Smad-independent mitogen activated protein kinase (MAPK) pathways are expressed in the nephron progenitor cell compartment and may be activated by BMPs, but that cortical interstitium may only be able to respond to BMPs through MAPK signaling. Localization of phosphorylated Smad transcription factors and studies of a BMP reporter mouse strain however indicate limited transcriptional responsiveness to Smad-mediated signaling in cap mesenchyme. An overview of genetic inactivation, organ culture, and primary cell studies indicates that BMP signaling may elicit two important biological outcomes in the nephrogenic zone: survival of the cap mesenchyme, and the physical segregation of interstitial and progenitor cell compartments. Ongoing studies using a novel primary cell system that establishes the nephrogenic zone ex vivo are pursuing the concept that the balance between Smad-mediated and Smadindependent responses to BMP ligand may underlie these distinct outcomes.
Pediatr Nephrol (2011) 26:1491–1497 DOI 10.1007/s00467-011-1819-8 Received: 5 November 2010 / Revised: 4 January 2011 / Accepted: 25 January 2011 / Published online: 4 March 2011
