Disruption of Hox9,10,11 function results in cellular level lineage infidelity in the kidney

Keri A. Drake, Mike Adam, Robert Mahoney, S. Steven Potter

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Hox genes are important regulators of development. The 39 mammalian Hox genes have considerable functional overlap, greatly confounding their study. In this report, we generated mice with multiple combinations of paralogous and flanking Abd-B Hox gene mutations to investigate functional redundancies in kidney development. The resulting mice developed a number of kidney abnormalities, including hypoplasia, agenesis, and severe cysts, with distinct Hox functions observed in early metanephric kidney formation and nephron progenitor maintenance. Most surprising, however, was that extensive removal of Hox shared function in these kidneys resulted in cellular level lineage infidelity. Strikingly, mutant nephron tubules consisted of intermixed cells with proximal tubule, loop of Henle, and collecting duct identities, with some single cells expressing markers associated with more than one nephron segment. These results indicate that Hox genes are required for proper lineage selection/maintenance and full repression of genes involved in cell fate restriction in the developing kidney.

Original languageEnglish (US)
Article number6306
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint

Homeobox Genes
Nephrons
Kidney
Maintenance
Loop of Henle
Cysts
Mutation
Genes

ASJC Scopus subject areas

  • General

Cite this

Disruption of Hox9,10,11 function results in cellular level lineage infidelity in the kidney. / Drake, Keri A.; Adam, Mike; Mahoney, Robert; Potter, S. Steven.

In: Scientific Reports, Vol. 8, No. 1, 6306, 01.12.2018.

Research output: Contribution to journalArticle

Drake, Keri A. ; Adam, Mike ; Mahoney, Robert ; Potter, S. Steven. / Disruption of Hox9,10,11 function results in cellular level lineage infidelity in the kidney. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
@article{4108bfeb9e584657801e6db597154bf0,
title = "Disruption of Hox9,10,11 function results in cellular level lineage infidelity in the kidney",
abstract = "Hox genes are important regulators of development. The 39 mammalian Hox genes have considerable functional overlap, greatly confounding their study. In this report, we generated mice with multiple combinations of paralogous and flanking Abd-B Hox gene mutations to investigate functional redundancies in kidney development. The resulting mice developed a number of kidney abnormalities, including hypoplasia, agenesis, and severe cysts, with distinct Hox functions observed in early metanephric kidney formation and nephron progenitor maintenance. Most surprising, however, was that extensive removal of Hox shared function in these kidneys resulted in cellular level lineage infidelity. Strikingly, mutant nephron tubules consisted of intermixed cells with proximal tubule, loop of Henle, and collecting duct identities, with some single cells expressing markers associated with more than one nephron segment. These results indicate that Hox genes are required for proper lineage selection/maintenance and full repression of genes involved in cell fate restriction in the developing kidney.",
author = "Drake, {Keri A.} and Mike Adam and Robert Mahoney and Potter, {S. Steven}",
year = "2018",
month = "12",
day = "1",
doi = "10.1038/s41598-018-24782-5",
language = "English (US)",
volume = "8",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Disruption of Hox9,10,11 function results in cellular level lineage infidelity in the kidney

AU - Drake, Keri A.

AU - Adam, Mike

AU - Mahoney, Robert

AU - Potter, S. Steven

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Hox genes are important regulators of development. The 39 mammalian Hox genes have considerable functional overlap, greatly confounding their study. In this report, we generated mice with multiple combinations of paralogous and flanking Abd-B Hox gene mutations to investigate functional redundancies in kidney development. The resulting mice developed a number of kidney abnormalities, including hypoplasia, agenesis, and severe cysts, with distinct Hox functions observed in early metanephric kidney formation and nephron progenitor maintenance. Most surprising, however, was that extensive removal of Hox shared function in these kidneys resulted in cellular level lineage infidelity. Strikingly, mutant nephron tubules consisted of intermixed cells with proximal tubule, loop of Henle, and collecting duct identities, with some single cells expressing markers associated with more than one nephron segment. These results indicate that Hox genes are required for proper lineage selection/maintenance and full repression of genes involved in cell fate restriction in the developing kidney.

AB - Hox genes are important regulators of development. The 39 mammalian Hox genes have considerable functional overlap, greatly confounding their study. In this report, we generated mice with multiple combinations of paralogous and flanking Abd-B Hox gene mutations to investigate functional redundancies in kidney development. The resulting mice developed a number of kidney abnormalities, including hypoplasia, agenesis, and severe cysts, with distinct Hox functions observed in early metanephric kidney formation and nephron progenitor maintenance. Most surprising, however, was that extensive removal of Hox shared function in these kidneys resulted in cellular level lineage infidelity. Strikingly, mutant nephron tubules consisted of intermixed cells with proximal tubule, loop of Henle, and collecting duct identities, with some single cells expressing markers associated with more than one nephron segment. These results indicate that Hox genes are required for proper lineage selection/maintenance and full repression of genes involved in cell fate restriction in the developing kidney.

UR - http://www.scopus.com/inward/record.url?scp=85045925963&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045925963&partnerID=8YFLogxK

U2 - 10.1038/s41598-018-24782-5

DO - 10.1038/s41598-018-24782-5

M3 - Article

VL - 8

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 6306

ER -