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Updated: Aug 16, 2026
Isolation and Culture of Cells from the Nephrogenic Zone of the Embryonic Mouse Kidney
Published on: April 22, 2011
Inactivation of FGF8 in early mesoderm reveals an essential role in kidney development
Alan O Perantoni1, Olga Timofeeva, Florence Naillat
1Laboratory of Comparative Carcinogenesis, National Cancer Institute, NCI-Frederick, Frederick, MD 21702, USA.
Abstract:
To bypass the essential gastrulation function of Fgf8 and study its role in lineages of the primitive streak, we have used a new mouse line, T-Cre, to generate mouse embryos with pan-mesodermal loss of Fgf8 expression. Surprisingly, despite previous models in which Fgf8 has been assigned a pivotal role in segmentation/somite differentiation, Fgf8 is not required for these processes. However, mutant neonates display severe renal hypoplasia with deficient nephron formation. In mutant kidneys, aberrant cell death occurs within the metanephric mesenchyme (MM), particularly in the cortical nephrogenic zone, which provides the progenitors for recurring rounds of nephron formation. Prior to mutant morphological changes, Wnt4 and Lim1 expression, which is essential for nephrogenesis, is absent in MM. Furthermore, comparative analysis of Wnt4-null homozygotes reveals concomitant downregulation of Lim1 and diminished tubule formation. Our data support a model whereby FGF8 and WNT4 function in concert to induce the expression of Lim1 for MM survival and tubulogenesis.
Insights
Fibroblast growth factor 8 (Fgf8) is not essential for embryonic segmentation but is crucial for kidney development. Loss of Fgf8 leads to renal hypoplasia by disrupting metanephric mesenchyme survival and tubulogenesis.
Area of Science:
- Developmental biology
- Renal physiology
- Genetics
Background:
- Fibroblast growth factor 8 (Fgf8) is critical for embryonic development, particularly gastrulation.
- Previous studies suggested Fgf8 plays a key role in segmentation and somite differentiation.
Purpose of the Study:
- To investigate the role of Fgf8 in primitive streak lineages, bypassing its essential gastrulation function.
- To determine Fgf8's requirement in segmentation and kidney development.
Main Methods:
- Generation of mouse embryos with pan-mesodermal loss of Fgf8 expression using a T-Cre mouse line.
- Analysis of Fgf8's role in segmentation, somite differentiation, and renal development.
- Comparative analysis with Wnt4-null homozygotes.
Main Results:
- Fgf8 is not required for segmentation or somite differentiation.
- Mutant embryos exhibit severe renal hypoplasia and deficient nephron formation.
- Aberrant cell death occurs in the metanephric mesenchyme (MM), with absence of Wnt4 and Lim1 expression prior to morphological changes.
- Wnt4 deficiency also leads to Lim1 downregulation and diminished tubule formation.
Conclusions:
- Fgf8 is dispensable for segmentation but essential for kidney development.
- FGF8 and WNT4 act synergistically to induce Lim1 expression, promoting MM survival and tubulogenesis.
- This study reveals a novel pathway for renal development involving FGF8 and WNT4 signaling.
