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Isolation and Culture of Cells from the Nephrogenic Zone of the Embryonic Mouse Kidney
Published on: April 22, 2011
A Hox-Eya-Pax complex regulates early kidney developmental gene expression
Ke-Qin Gong1, Alisha R Yallowitz, Hanshi Sun
1Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical Center, 109 Zina Pitcher, 3045 BSRB, Ann Arbor, MI 48109-2200, USA.
Molecular and Cellular Biology
|September 6, 2007
Summary
Hox11 proteins complex with Pax2 and Eya1 to activate Six2 and Gdnf gene expression, crucial for kidney development. This interaction is essential for Six2 expression in vivo, highlighting a key pathway in embryonic kidney formation.
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- Hox genes specify the anterior-posterior body axis during embryonic development.
- Hox proteins require cofactors due to their limited DNA binding specificity.
- Identifying Hox regulatory partners and target genes is crucial for understanding developmental processes.
Purpose of the Study:
- To identify regulatory partners and downstream targets of Hox11 proteins in kidney development.
- To elucidate the mechanism by which Hox11 proteins regulate gene expression in the metanephric mesenchyme.
Main Methods:
- Co-immunoprecipitation to identify protein complexes.
- Reporter assays to assess gene activation.
- In vivo studies to evaluate the necessity of identified binding sites for gene expression.
Main Results:
- Hox11 paralogs form a complex with Pax2 and Eya1.
- This complex directly activates the expression of Six2 and Gdnf in the metanephric mesenchyme.
- A specific binding site in the Six2 enhancer is essential for Hox11-Eya1-Pax2-mediated activation and Six2 expression in vivo.
- Genetic interactions support Hox11 and Eya1 acting in the same developmental pathway.
Conclusions:
- Anterior-posterior-patterning Hox proteins interact with Pax2 and Eya1 to regulate key genes in kidney development.
- This interaction directly activates downstream targets like Six2 and Gdnf.
- The findings reveal a novel mechanism for Hox proteins in nephrogenesis and anterior-posterior patterning.
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