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2017 ; 424
(1
): 77-89
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gab.com Text
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English Wikipedia
Elf5 is a principal cell lineage specific transcription factor in the kidney that
contributes to Aqp2 and Avpr2 gene expression
#MMPMID28215940
Grassmeyer J
; Mukherjee M
; deRiso J
; Hettinger C
; Bailey M
; Sinha S
; Visvader JE
; Zhao H
; Fogarty E
; Surendran K
Dev Biol
2017[Apr]; 424
(1
): 77-89
PMID28215940
show ga
The mammalian kidney collecting ducts are critical for water, electrolyte and
acid-base homeostasis and develop as a branched network of tubular structures
composed of principal cells intermingled with intercalated cells. The
intermingled nature of the different collecting duct cell types has made it
challenging to identify unique and critical factors that mark and/or regulate the
development of the different collecting duct cell lineages. Here we report that
the canonical Notch signaling pathway components, RBPJ and Presinilin1 and 2, are
involved in patterning the mouse collecting duct cell fates by maintaining a
balance between principal cell and intercalated cell fates. The relatively
reduced number of principal cells in Notch-signaling-deficient kidneys offered a
unique genetic leverage to identify critical principal cell-enriched factors by
transcriptional profiling. Elf5, which codes for an ETS transcription factor, is
one such gene that is down-regulated in kidneys with Notch-signaling-deficient
collecting ducts. Additionally, Elf5 is among the earliest genes up regulated by
ectopic expression of activated Notch1 in the developing collecting ducts. In the
kidney, Elf5 is first expressed early within developing collecting ducts and
remains on in mature principal cells. Lineage tracing of Elf5-expressing cells
revealed that they are committed to the principal cell lineage by as early as
E16.5. Over-expression of ETS Class IIa transcription factors, including Elf5,
Elf3 and Ehf, increase the transcriptional activity of the proximal promoters of
Aqp2 and Avpr2 in cultured ureteric duct cell lines. Conditional inactivation of
Elf5 in the developing collecting ducts results in a small but significant
reduction in the expression levels of Aqp2 and Avpr2 genes. We have identified
Elf5 as an early maker of the principal cell lineage that contributes to the
expression of principal cell specific genes.