First published online June 11, 2007
Development 134, 1305e (2007)
© The Company of Biologists Limited
Kidney development: an invasion of space
Reciprocal interactions between the ureteric bud (UB) and the surrounding
metanephric mesenchyme (MM) are crucial for kidney induction and development.
Louis Reichardt's group have previously shown that, in the absence of
8ß1 integrin (Itga8) expression in the MM, the UB fails
to invade the surrounding MM - the first step in kidney induction - causing
kidney agenesis. Now, this group identifies nephronectin (Npnt) as
8ß1 integrin's essential ligand. Npnt is expressed in the UB and
mediates 8ß1 integrin activity during early mouse kidney
development (see p.
2501). The expression of glial cell line-derived growth factor (GDNF)
- an important growth factor in kidney development - in the MM, they show, is
stimulated in response to Npnt/8ß1 integrin activity. Using
Npnt-null and Itga8-null mice, these researchers show that,
in both strains, UBs form but fail to invade the MM, as Gdnf
expression is reduced. However, their other findings reveal that additional
factors may contribute to normal Gdnf expression patterns during
kidney development. One such factor is revealed in a study by Rolf Zeller's
group on p. 2397, who
report that gremlin 1 (Grem1), a BMP antagonist, is upregulated in
the mouse MM prior to UB outgrowth. The resultant reduction in Bmp4 activity
establishes the epithelial-mesenchymal (e-m) Gdnf/Wnt11 autoregulatory
feedback loop that is essential for the UB's initial outgrowth and branching.
Moreover, they show that failed UB outgrowth and secondary branching can be
rescued in cultured gremlin mutant kidney primordia by recombinant
gremlin. Wnt11 expression at the epithelial tips and Gdnf
expression in the MM is also restored by gremlin in these cultures. The
regulation of Bmp4 activity by gremlin, and the subsequent establishment of
the e-m feedback loop, provides insight into the mechanisms that mediate the
UB's invasion of the MM, the important first step in kidney development.
Further insights in kidney development are also reported by Andrew McMahon's
group on p. 2533, who
reveal that, at a later stage of kidney development, Wnt9b and Wnt4 signalling
act via carefully modulated ß-catenin-mediated canonical signalling
during renal vesicle induction and mesenchymal-epithelial transition.
Related articles in Development:
- Reduction of BMP4 activity by gremlin 1 enables ureteric bud outgrowth and GDNF/WNT11 feedback signalling during kidney branching morphogenesis
- Odyssé Michos, Alexandre Gonçalves, Javier Lopez-Rios, Eva Tiecke, Florence Naillat, Konstantin Beier, Antonella Galli, Seppo Vainio, and Rolf Zeller
Development 2007 134: 2397-2405.
[Abstract]
[Full Text]
- The ECM protein nephronectin promotes kidney development via integrin 8ß1-mediated stimulation of Gdnf expression
- James M. Linton, Gail R. Martin, and Louis F. Reichardt
Development 2007 134: 2501-2509.
[Abstract]
[Full Text]
- Wnt/ß-catenin signaling regulates nephron induction during mouse kidney development
- Joo-Seop Park, M. Todd Valerius, and Andrew P. McMahon
Development 2007 134: 2533-2539.
[Abstract]
[Full Text]
