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The evolutionary origin of the Runx/CBFbeta transcription factors--studies of the most basal metazoans.

Sullivan JC, Sher D, Eisenstein M, Shigesada K, Reitzel AM, Marlow H, Levanon D, Groner Y, Finnerty JR, Gat U - BMC Evol. Biol. (2008)

Bottom Line: Comparative structural modeling indicates that the Runx-CBFbeta-DNA complex from most cnidarians and sponges is highly similar to that found in humans, with changes in the residues involved in Runx-CBFbeta dimerization in either of the proteins mirrored by compensatory changes in the binding partner.These results reveal that Runx and CBFbeta likely functioned together to regulate transcription in the common ancestor of all metazoans, and the structure of the Runx-CBFbeta-DNA complex has remained extremely conserved since the human-sponge divergence.The expression data suggest a hypothesis that these genes may have played a role in nerve cell differentiation or maintenance in the common ancestor of cnidarians and bilaterians.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biology, Boston University, 5 Cummington St, Boston, MA 02215, USA. jamescsullivan@gmail.com

ABSTRACT

Background: Members of the Runx family of transcriptional regulators, which bind DNA as heterodimers with CBFbeta, are known to play critical roles in embryonic development in many triploblastic animals such as mammals and insects. They are known to regulate basic developmental processes such as cell fate determination and cellular potency in multiple stem-cell types, including the sensory nerve cell progenitors of ganglia in mammals.

Results: In this study, we detect and characterize the hitherto unexplored Runx/CBFbeta genes of cnidarians and sponges, two basal animal lineages that are well known for their extensive regenerative capacity. Comparative structural modeling indicates that the Runx-CBFbeta-DNA complex from most cnidarians and sponges is highly similar to that found in humans, with changes in the residues involved in Runx-CBFbeta dimerization in either of the proteins mirrored by compensatory changes in the binding partner. In situ hybridization studies reveal that Nematostella Runx and CBFbeta are expressed predominantly in small isolated foci at the base of the ectoderm of the tentacles in adult animals, possibly representing neurons or their progenitors.

Conclusion: These results reveal that Runx and CBFbeta likely functioned together to regulate transcription in the common ancestor of all metazoans, and the structure of the Runx-CBFbeta-DNA complex has remained extremely conserved since the human-sponge divergence. The expression data suggest a hypothesis that these genes may have played a role in nerve cell differentiation or maintenance in the common ancestor of cnidarians and bilaterians.

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Expression pattern of Nv-CBFβ in adult Nematostella. A Digoxygenin-labeled riboprobe corresponding to nucleotides 56–434 was used. A) CBFβ is expressed in the tentacles and mouth region of adult anemones. No staining could be seen when a control probe from the sense strand was used (right animal). B) An inset from A, showing strong expression in the tentacle tips (arrow). C) Expression of CBFβ in the mouth and extended upper pharynx of the same animal as depicted in A and B. Expression levels in the mouth region differed between different animals. D) General architecture of the tentacles and mouth region, showing the location of the enlarged micrographs in E and H (panel H is of a different serial section from the same anemone). Ten = tentacle, phx = pharynx. Scale bar = 100 μm. E, F) Expression of CBFβ at the base of the ectoderm of the tentacles (arrowheads) en = endoderm, ec = ectoderm, mes-mesoglea. Bar in E = 100 μm, in F = 20 μm. G) Expression of CBFβ in the ectoderm of the mouth (arrows). en = endoderm, ec = ectoderm, mes-mesoglea, gvc = gastrovascular cavity. Bar = 100 μm H) Enlargement of a region in the mouth, showing the CBFβ expression in cells close to large microbasic mastigophore nematocysts (arrowheads) Bar = 20 μm. I) Thin (2 μm) epoxy cross section through the mouth region stained with Methylene Blue, revealing the secretory gland cells (gc) and abundance of microbasic mastigophore nematocytes (mbm) of different sizes. Bar = 20 μm.
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Figure 8: Expression pattern of Nv-CBFβ in adult Nematostella. A Digoxygenin-labeled riboprobe corresponding to nucleotides 56–434 was used. A) CBFβ is expressed in the tentacles and mouth region of adult anemones. No staining could be seen when a control probe from the sense strand was used (right animal). B) An inset from A, showing strong expression in the tentacle tips (arrow). C) Expression of CBFβ in the mouth and extended upper pharynx of the same animal as depicted in A and B. Expression levels in the mouth region differed between different animals. D) General architecture of the tentacles and mouth region, showing the location of the enlarged micrographs in E and H (panel H is of a different serial section from the same anemone). Ten = tentacle, phx = pharynx. Scale bar = 100 μm. E, F) Expression of CBFβ at the base of the ectoderm of the tentacles (arrowheads) en = endoderm, ec = ectoderm, mes-mesoglea. Bar in E = 100 μm, in F = 20 μm. G) Expression of CBFβ in the ectoderm of the mouth (arrows). en = endoderm, ec = ectoderm, mes-mesoglea, gvc = gastrovascular cavity. Bar = 100 μm H) Enlargement of a region in the mouth, showing the CBFβ expression in cells close to large microbasic mastigophore nematocysts (arrowheads) Bar = 20 μm. I) Thin (2 μm) epoxy cross section through the mouth region stained with Methylene Blue, revealing the secretory gland cells (gc) and abundance of microbasic mastigophore nematocytes (mbm) of different sizes. Bar = 20 μm.

Mentions: Similar to Runx, CBFβ is expressed in the tentacle ectoderm, with the strongest staining in the tentacle tips (Figure 8, panels A-C). Also like Runx, the CBFβ-expressing cells are located primarily in the basal layer of the ectoderm and in close association with large microbasic mastigophore nematocytes, which are a major component of this cell-rich region of the animal (Figure 8. panels F-H). However, in contrast to Runx, some of the individual animals assayed also expressed CBFβ in the mouth region (Figure 8, panels D, G, and H).


The evolutionary origin of the Runx/CBFbeta transcription factors--studies of the most basal metazoans.

Sullivan JC, Sher D, Eisenstein M, Shigesada K, Reitzel AM, Marlow H, Levanon D, Groner Y, Finnerty JR, Gat U - BMC Evol. Biol. (2008)

Expression pattern of Nv-CBFβ in adult Nematostella. A Digoxygenin-labeled riboprobe corresponding to nucleotides 56–434 was used. A) CBFβ is expressed in the tentacles and mouth region of adult anemones. No staining could be seen when a control probe from the sense strand was used (right animal). B) An inset from A, showing strong expression in the tentacle tips (arrow). C) Expression of CBFβ in the mouth and extended upper pharynx of the same animal as depicted in A and B. Expression levels in the mouth region differed between different animals. D) General architecture of the tentacles and mouth region, showing the location of the enlarged micrographs in E and H (panel H is of a different serial section from the same anemone). Ten = tentacle, phx = pharynx. Scale bar = 100 μm. E, F) Expression of CBFβ at the base of the ectoderm of the tentacles (arrowheads) en = endoderm, ec = ectoderm, mes-mesoglea. Bar in E = 100 μm, in F = 20 μm. G) Expression of CBFβ in the ectoderm of the mouth (arrows). en = endoderm, ec = ectoderm, mes-mesoglea, gvc = gastrovascular cavity. Bar = 100 μm H) Enlargement of a region in the mouth, showing the CBFβ expression in cells close to large microbasic mastigophore nematocysts (arrowheads) Bar = 20 μm. I) Thin (2 μm) epoxy cross section through the mouth region stained with Methylene Blue, revealing the secretory gland cells (gc) and abundance of microbasic mastigophore nematocytes (mbm) of different sizes. Bar = 20 μm.
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Related In: Results  -  Collection

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Figure 8: Expression pattern of Nv-CBFβ in adult Nematostella. A Digoxygenin-labeled riboprobe corresponding to nucleotides 56–434 was used. A) CBFβ is expressed in the tentacles and mouth region of adult anemones. No staining could be seen when a control probe from the sense strand was used (right animal). B) An inset from A, showing strong expression in the tentacle tips (arrow). C) Expression of CBFβ in the mouth and extended upper pharynx of the same animal as depicted in A and B. Expression levels in the mouth region differed between different animals. D) General architecture of the tentacles and mouth region, showing the location of the enlarged micrographs in E and H (panel H is of a different serial section from the same anemone). Ten = tentacle, phx = pharynx. Scale bar = 100 μm. E, F) Expression of CBFβ at the base of the ectoderm of the tentacles (arrowheads) en = endoderm, ec = ectoderm, mes-mesoglea. Bar in E = 100 μm, in F = 20 μm. G) Expression of CBFβ in the ectoderm of the mouth (arrows). en = endoderm, ec = ectoderm, mes-mesoglea, gvc = gastrovascular cavity. Bar = 100 μm H) Enlargement of a region in the mouth, showing the CBFβ expression in cells close to large microbasic mastigophore nematocysts (arrowheads) Bar = 20 μm. I) Thin (2 μm) epoxy cross section through the mouth region stained with Methylene Blue, revealing the secretory gland cells (gc) and abundance of microbasic mastigophore nematocytes (mbm) of different sizes. Bar = 20 μm.
Mentions: Similar to Runx, CBFβ is expressed in the tentacle ectoderm, with the strongest staining in the tentacle tips (Figure 8, panels A-C). Also like Runx, the CBFβ-expressing cells are located primarily in the basal layer of the ectoderm and in close association with large microbasic mastigophore nematocytes, which are a major component of this cell-rich region of the animal (Figure 8. panels F-H). However, in contrast to Runx, some of the individual animals assayed also expressed CBFβ in the mouth region (Figure 8, panels D, G, and H).

Bottom Line: Comparative structural modeling indicates that the Runx-CBFbeta-DNA complex from most cnidarians and sponges is highly similar to that found in humans, with changes in the residues involved in Runx-CBFbeta dimerization in either of the proteins mirrored by compensatory changes in the binding partner.These results reveal that Runx and CBFbeta likely functioned together to regulate transcription in the common ancestor of all metazoans, and the structure of the Runx-CBFbeta-DNA complex has remained extremely conserved since the human-sponge divergence.The expression data suggest a hypothesis that these genes may have played a role in nerve cell differentiation or maintenance in the common ancestor of cnidarians and bilaterians.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biology, Boston University, 5 Cummington St, Boston, MA 02215, USA. jamescsullivan@gmail.com

ABSTRACT

Background: Members of the Runx family of transcriptional regulators, which bind DNA as heterodimers with CBFbeta, are known to play critical roles in embryonic development in many triploblastic animals such as mammals and insects. They are known to regulate basic developmental processes such as cell fate determination and cellular potency in multiple stem-cell types, including the sensory nerve cell progenitors of ganglia in mammals.

Results: In this study, we detect and characterize the hitherto unexplored Runx/CBFbeta genes of cnidarians and sponges, two basal animal lineages that are well known for their extensive regenerative capacity. Comparative structural modeling indicates that the Runx-CBFbeta-DNA complex from most cnidarians and sponges is highly similar to that found in humans, with changes in the residues involved in Runx-CBFbeta dimerization in either of the proteins mirrored by compensatory changes in the binding partner. In situ hybridization studies reveal that Nematostella Runx and CBFbeta are expressed predominantly in small isolated foci at the base of the ectoderm of the tentacles in adult animals, possibly representing neurons or their progenitors.

Conclusion: These results reveal that Runx and CBFbeta likely functioned together to regulate transcription in the common ancestor of all metazoans, and the structure of the Runx-CBFbeta-DNA complex has remained extremely conserved since the human-sponge divergence. The expression data suggest a hypothesis that these genes may have played a role in nerve cell differentiation or maintenance in the common ancestor of cnidarians and bilaterians.

Show MeSH
Related in: MedlinePlus