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Hox11 paralogous genes are essential for metanephric kidney induction
Deneen M Wellik1, Patrick J Hawkes, Mario R Capecchi
1Department of Human Genetics and Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City 84112-5331, USA.
Genes & Development
|June 7, 2002
Summary
Loss of Hox11 genes prevents kidney formation by disrupting the Six2 and Gdnf pathway. This reveals a critical role for Hox11 genes in metanephric kidney development.
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- Mammalian Hox genes are crucial for development and are organized into four linkage groups.
- Paralogous Hox genes exhibit functional redundancy, making analysis of single or double mutants challenging.
- Previous studies showed Hoxa11/Hoxd11 double mutants have kidney hypoplasia, indicating a role for Hox11 genes in kidney development.
Purpose of the Study:
- To investigate the role of the Hox11 paralogous genes, including Hoxc11, in mammalian kidney development.
- To elucidate the molecular mechanisms by which Hox11 genes regulate metanephric kidney induction.
Main Methods:
- Generation and analysis of Hoxa11/Hoxc11/Hoxd11 triple mutant mice.
- Molecular analysis of gene expression patterns in mutant kidneys, focusing on early patterning genes and signaling molecules.
Main Results:
- Triple Hox11 mutants exhibit a complete loss of metanephric kidney induction.
- Early patterning genes (Pax2, Wt1, Eya1) were expressed, but Six2 and the inducing growth factor Gdnf were absent.
- Absence of Gdnf led to a failure in ureteric bud formation.
Conclusions:
- Hox11 genes are essential for initiating metanephric kidney induction.
- Hox11 controls kidney development by interacting with the Pax-Eya-Six regulatory cascade.
- This regulatory pathway involving Hox genes may be broadly utilized for inducing structures along the anteroposterior axis.