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Mutational analysis of genes with ureteric progenitor cell‐specific expression in branching morphogenesis of the mouse kidney
Author(s) -
Rutledge Elisabeth A.,
McMahon Andrew P.
Publication year - 2020
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.157
Subject(s) - ureteric bud , biology , kidney development , progenitor cell , nephron , phenotype , mutant , kidney , progenitor , penetrance , ureter , gene , microbiology and biotechnology , genetics , stem cell , embryonic stem cell , medicine , urology
Background Ureteric progenitor cells (UPCs) within the branch tips of the arborizing ureteric epithelium of the kidney's developing collecting system establish the shape and cellular organization of the collecting network, and drive the nephrogenic program through their interactions with nephron progenitor cells. In a previous study, expression screening identified a cohort of genes showing UPC‐enriched expression including D17H6S56E‐5 , Hs3st3a1 , Hs3st3b1 , and Tmem59l . Each of these is also enriched in branch tips of assembling airways of the developing lungs. Here, we used Crispr‐CAS9 directed gene editing to mutate each of these targets to address their potential role(s) in UPC programs. Results Single ( D17H6S56E‐5 and Tmem59 l) and double ( Hs3st3a1 and Hs3st3b1 ) mutants were viable, fertile, and displayed varying frequencies of ureter duplications and no overt lung phenotype. Ureter duplications arise spontaneously through multiple outgrowths of the ureteric bud at the onset of kidney development. Tmem59l mutants and Hs3st3a1 / Hs3st3b1 compound mutants showed a weakly penetrant, but statistically significant increase in duplicated ureters compared to C57BL6/J and SW wild‐type mouse strains. Conclusions Tmem59l and Hs3st3a1 / Hs3st3b1 activities contribute to the regulatory programs restricting ureteric outgrowth in the developing mouse kidney. However, the low penetrance of the observed phenotype precludes a detailed analysis of their specific actions.