1. Expected and Unexpected Expression of Gdnf in Kidney Progenitor Cells
- Author
-
Hammond, Benjamin
- Subjects
- Developmental Biology, Gdnf, Nephric Duct, Nephric Cord, Progenitor Cells, Kidney Development
- Abstract
It has been established that the early presence of Glial cell line-derived neurotrophic factor (GDNF) in the metanephric mesenchyme is essential for the outgrowth of the ureteric bud from the nephric duct. Also, GDNF in the cap mesenchyme promotes branching of the collecting duct throughout kidney development. We have shown that GNDF is expressed by self-renewing nephron progenitor cells (NPCs) at mouse embryonic day 10.5 (E10.5); however, single-cell RNAseq by Magella et al., demonstrated that Gdnf is strongly expressed by stromal progenitor cells at E14.5. To reconcile these seemingly opposed results, we used a transgenic GDNF-CreERT2 and R26R-tdTomato mouse model to conduct lineage tracing experiments activated through tamoxifen injections at different time points during development. We hypothesized that the expression of Gdnf was dynamic, with early expression in NPCs transitioning into stromal progenitors at later stages. Our lineage studies demonstrate that Gdnf is expressed primarily by NPCs at early stages (from E9.5 to E12.5) and primarily by stromal cells during the later stages of development (E13.5 and later). Unexpectedly, we revealed that Gdnf is also expressed by nephric duct (ND) progenitors at even earlier stages. Expression of Gdnf was transient in the ND, and quantification of recombination shows that expression in the ND progenitors starts as early as E7.5 and peaks around E8.5. Altogether, our results indicate that Gdnf is expressed by all kidney progenitor cells (ND progenitors, NPCs, and stromal progenitors) but at different time points during kidney development. The physiological relevance of these transitions remains to be elucidated.
- Published
- 2023