---
_id: '9707'
abstract:
- lang: eng
text: Branching morphogenesis of the epithelial ureteric bud forms the renal collecting
duct system and is critical for normal nephron number, while low nephron number
is implicated in hypertension and renal disease. Ureteric bud growth and branching
requires GDNF signaling from the surrounding mesenchyme to cells at the ureteric
bud tips, via the Ret receptor tyrosine kinase and coreceptor Gfrα1; Ret signaling
up-regulates transcription factors Etv4 and Etv5, which are also critical for
branching. Despite extensive knowledge of the genetic control of these events,
it is not understood, at the cellular level, how renal branching morphogenesis
is achieved or how Ret signaling influences epithelial cell behaviors to promote
this process. Analysis of chimeric embryos previously suggested a role for Ret
signaling in promoting cell rearrangements in the nephric duct, but this method
was unsuited to study individual cell behaviors during ureteric bud branching.
Here, we use Mosaic Analysis with Double Markers (MADM), combined with organ culture
and time-lapse imaging, to trace the movements and divisions of individual ureteric
bud tip cells. We first examine wild-type clones and then Ret or Etv4 mutant/wild-type
clones in which the mutant and wild-type sister cells are differentially and heritably
marked by green and red fluorescent proteins. We find that, in normal kidneys,
most individual tip cells behave as self-renewing progenitors, some of whose progeny
remain at the tips while others populate the growing UB trunks. In Ret or Etv4
MADM clones, the wild-type cells generated at a UB tip are much more likely to
remain at, or move to, the new tips during branching and elongation, while their
Ret−/− or Etv4−/− sister cells tend to lag behind and contribute only to the trunks.
By tracking successive mitoses in a cell lineage, we find that Ret signaling has
little effect on proliferation, in contrast to its effects on cell movement. Our
results show that Ret/Etv4 signaling promotes directed cell movements in the ureteric
bud tips, and suggest a model in which these cell movements mediate branching
morphogenesis.
article_processing_charge: No
author:
- first_name: Paul
full_name: Riccio, Paul
last_name: Riccio
- first_name: Christina
full_name: Cebrián, Christina
last_name: Cebrián
- first_name: Hui
full_name: Zong, Hui
last_name: Zong
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Frank
full_name: Costantini, Frank
last_name: Costantini
citation:
ama: 'Riccio P, Cebrián C, Zong H, Hippenmeyer S, Costantini F. Data from: Ret and
Etv4 promote directed movements of progenitor cells during renal branching morphogenesis.
2017. doi:10.5061/dryad.pk16b'
apa: 'Riccio, P., Cebrián, C., Zong, H., Hippenmeyer, S., & Costantini, F. (2017).
Data from: Ret and Etv4 promote directed movements of progenitor cells during
renal branching morphogenesis. Dryad. https://doi.org/10.5061/dryad.pk16b'
chicago: 'Riccio, Paul, Christina Cebrián, Hui Zong, Simon Hippenmeyer, and Frank
Costantini. “Data from: Ret and Etv4 Promote Directed Movements of Progenitor
Cells during Renal Branching Morphogenesis.” Dryad, 2017. https://doi.org/10.5061/dryad.pk16b.'
ieee: 'P. Riccio, C. Cebrián, H. Zong, S. Hippenmeyer, and F. Costantini, “Data
from: Ret and Etv4 promote directed movements of progenitor cells during renal
branching morphogenesis.” Dryad, 2017.'
ista: 'Riccio P, Cebrián C, Zong H, Hippenmeyer S, Costantini F. 2017. Data from:
Ret and Etv4 promote directed movements of progenitor cells during renal branching
morphogenesis, Dryad, 10.5061/dryad.pk16b.'
mla: 'Riccio, Paul, et al. Data from: Ret and Etv4 Promote Directed Movements
of Progenitor Cells during Renal Branching Morphogenesis. Dryad, 2017, doi:10.5061/dryad.pk16b.'
short: P. Riccio, C. Cebrián, H. Zong, S. Hippenmeyer, F. Costantini, (2017).
date_created: 2021-07-23T09:39:34Z
date_published: 2017-01-14T00:00:00Z
date_updated: 2022-08-25T13:34:55Z
day: '14'
department:
- _id: SiHi
doi: 10.5061/dryad.pk16b
main_file_link:
- open_access: '1'
url: https://doi.org/10.5061/dryad.pk16b
month: '01'
oa: 1
oa_version: Published Version
publisher: Dryad
related_material:
record:
- id: '9702'
relation: used_in_publication
status: deleted
status: public
title: 'Data from: Ret and Etv4 promote directed movements of progenitor cells during
renal branching morphogenesis'
type: research_data_reference
user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf
year: '2017'
...