Heliot, C., Desgrange, A., Buisson, I., Prunskaite-Hyyrylainen, R., Shan, J., Vainio, S., Umbhauer, M., Cereghini, S. (2013) HNF1B controls proximal-intermediate nephron segment identity in vertebrates by regulating Notch signalling components and Irx1/2. Development, 140 (4), 873-885. doi:doi: 10.1242/dev.086538
HNF1B controls proximal-intermediate nephron segment identity in vertebrates by regulating Notch signalling components and Irx1/2
|Author:||Heliot, Claire1,2,3; Desgrange, Audrey1,2,3; Buisson, Isabelle2,3;|
1Inserm Unité 969, 9 quai St Bernard Bat. C, 75005 Paris, France
2CNRS, UMR7622 Developmental Biology, 9 quai St Bernard Bat. C, 75005 Paris, France
3Université Pierre et Marie Curie, UMR7622 Developmental Biology, 9 quai St Bernard Bat. C, 75005 Paris, France
4Oulu Centre for Cell-Matrix Research, Department of Medical Biochemistry and Molecular Biology, Institute of Biomedicine, Biocenter Oulu and Laboratory of Developmental Biology, University of Oulu, PO Box 5000, FIN-90014, Finland
|Online Access:||PDF Full Text (PDF, 6.4 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2020051126029
Company of Biologists,
|Publish Date:|| 2020-05-11
The nephron is a highly specialised segmented structure that provides essential filtration and resorption renal functions. It arises by formation of a polarised renal vesicle that differentiates into a comma-shaped body and then a regionalised S-shaped body (SSB), with the main prospective segments mapped to discrete domains. The regulatory circuits involved in initial nephron patterning are poorly understood. We report here that HNF1B, a transcription factor known to be involved in ureteric bud branching and initiation of nephrogenesis, has an additional role in segment fate acquisition. Hnf1b conditional inactivation in murine nephron progenitors results in rudimentary nephrons comprising a glomerulus connected to the collecting system by a short tubule displaying distal fates. Renal vesicles develop and polarise normally but fail to progress to correctly patterned SSBs. Major defects are evident at late SSBs, with altered morphology, reduction of a proximo-medial subdomain and increased apoptosis. This is preceded by strong downregulation of the Notch pathway components Lfng, Dll1 and Jag1 and the Irx1/2 factors, which are potential regulators of proximal and Henle’s loop segment fates. Moreover, HNF1B is recruited to the regulatory sequences of most of these genes. Overexpression of a HNF1B dominant-negative construct in Xenopus embryos causes downregulation specifically of proximal and intermediate pronephric segment markers. These results show that HNF1B is required for the acquisition of a proximo-intermediate segment fate in vertebrates, thus uncovering a previously unappreciated function of a novel SSB subcompartment in global nephron segmentation and further differentiation.
|Pages:||873 - 885|
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
1182 Biochemistry, cell and molecular biology
This work was supported by EuReGene [contract LSHG-CT-2004 005 085]; Agence National de la Recherche [ANR Blan06-2_139420]; GIS Maladies Rares; EU FP7 (Marie Curie Initial Training Network BOLD: Biology of Liver and the Pancreatic Development and Disease) and the Institut National de la Santé et de la Recherche Médicale (INSERM) (grants to S.C.); and by Centre National de la Recherche Scientifique (CNRS) and Université Pierre et Marie Curie (grants to S.C. and M.U.). C.H. and A.D. are recipients of PhD student fellowships from the Ministère de la Recherche. C.H. was also recipient a PhD student fellowship from the Association pour la Recherche sur le Cancer (ARC). S.V. was supported by Sigrid Jusélius Foundation, Academy of Finland (AF) [206038, 121647], AF Centre of Excellence and FiDiPro programs [251314; 263246], and by the EUNephrOmics, FP-7-Health-2012-Innovation, the EURenOmics 305608.
|Academy of Finland Grant Number:||
206038 (Academy of Finland Funding decision)
121647 (Academy of Finland Funding decision)
251314 (Academy of Finland Funding decision)
263246 (Academy of Finland Funding decision)
© 2013. Published by The Company of Biologists Ltd.