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A Hox-Eya-Pax complex regulates early kidney developmental gene expression.

ABSTRACT: During embryonic development, the anterior-posterior body axis is specified in part by the combinatorial activities of Hox genes. Given the poor DNA binding specificity of Hox proteins, their interaction with cofactors to regulate target genes is critical. However, few regulatory partners or downstream target genes have been identified. Herein, we demonstrate that Hox11 paralogous proteins form a complex with Pax2 and Eya1 to directly activate expression of Six2 and Gdnf in the metanephric mesenchyme. We have identified the binding site within the Six2 enhancer necessary for Hox11-Eya1-Pax2-mediated activation and demonstrate that this site is essential for Six2 expression in vivo. Furthermore, genetic interactions between Hox11 and Eya1 are consistent with their participation in the same pathway. Thus, anterior-posterior-patterning Hox proteins interact with Pax2 and Eya1, factors important for nephrogenic mesoderm specification, to directly regulate the activation of downstream target genes during early kidney development.

SUBMITTER: Gong KQ

PROVIDER: S-EPMC2169072 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature

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A Hox-Eya-Pax complex regulates early kidney developmental gene expression.

Gong Ke-Qin KQ Yallowitz Alisha R AR Sun Hanshi H Dressler Gregory R GR Wellik Deneen M DM

Molecular and cellular biology 20070904 21

During embryonic development, the anterior-posterior body axis is specified in part by the combinatorial activities of Hox genes. Given the poor DNA binding specificity of Hox proteins, their interaction with cofactors to regulate target genes is critical. However, few regulatory partners or downstream target genes have been identified. Herein, we demonstrate that Hox11 paralogous proteins form a complex with Pax2 and Eya1 to directly activate expression of Six2 and Gdnf in the metanephric mesen ...[more]

PMID: 17785448

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Project description:BackgroundThe Pax-Six-Eya-Dach network (PSEDN) is involved in a variety of developmental processes, including well documented roles in determination of sensory organs and morphogenesis in bilaterian animals. Expression of PSEDN components in cnidarians is consistent with function in sensory organ development. Recent work in demosponges demonstrated the presence of single homologs of Pax and Six genes, and their possible involvement in morphogenesis, but the absence of the remaining network components. Calcisponges are evolutionarily distant from demosponges, and the developmental toolkits of these two lineages differ significantly. We used an emerging model system, Sycon ciliatum, to identify components of the PSEDN and study their expression during embryonic and postembryonic development.ResultsWe identified two Pax, three Six and one Eya genes in calcisponges, a situation strikingly different than in the previously studied demosponges. One of the calcisponge Pax genes can be identified as PaxB, while the second Pax gene has no clear affiliation. The three calcisponge Six genes could not be confidently classified within any known family of Six genes. Expression analysis in adult S. ciliatum demonstrated that representatives of Pax, Six and Eya are expressed in patterns consistent with roles in morphogenesis of the choanocyte chambers. Distinct paralogues of Pax and Six genes were expressed early in the development of the putative larval sensory cells, the cruciform cells. While lack of known photo pigments in calcisponge genomes precludes formal assignment of function to the cruciform cells, we also show that they express additional eumetazoan genes involved in specification of sensory and neuronal cells: Elav and Msi.ConclusionsOur results indicate that the role of a Pax-Six-Eya network in morphogenesis likely predates the animal divergence. In addition, Pax and Six, as well as Elav and Msi are expressed during differentiation of cruciform cells, which are good candidates for being sensory cells of the calcaronean sponge larvae.

Dataset Information

A Hox-Eya-Pax complex regulates early kidney developmental gene expression.

Publications

A Hox-Eya-Pax complex regulates early kidney developmental gene expression.

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