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Tbx2a is required for specification of endodermal pouches during development of the pharyngeal arches.

Thi Thu HN, Haw Tien SF, Loh SL, Bok Yan JS, Korzh V - PLoS ONE (2013)

Bottom Line: While tbx2a expression is restricted to the endodermal pouches, its function is required for the normal morphogenesis of the entire pharyngeal arches.The use of bimolecular fluorescence complementation revealed the interaction between Tbx2a and Tbx1, thus providing support for the idea that functional interaction between different, co-expressed Tbx proteins could be a common theme across developmental processes in cell lineages and tissues.Together, this work provides mechanistic insight into the role of TBX2 in human disorders affecting the face and neck.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular and Cell Biology, Singapore, Singapore ; Department of Biological Sciences, National University of Singapore, Singapore, Singapore ; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

ABSTRACT
Tbx2 is a member of the T-box family of transcription factors essential for embryo- and organogenesis. A deficiency in the zebrafish paralogue tbx2a causes abnormalities of the pharyngeal arches in a p53-independent manner. The pharyngeal arches are formed by derivatives of all three embryonic germ layers: endodermal pouches, mesenchymal condensations and neural crest cells. While tbx2a expression is restricted to the endodermal pouches, its function is required for the normal morphogenesis of the entire pharyngeal arches. Given the similar function of Tbx1 in craniofacial development, we explored the possibility of an interaction between Tbx1 and Tbx2a. The use of bimolecular fluorescence complementation revealed the interaction between Tbx2a and Tbx1, thus providing support for the idea that functional interaction between different, co-expressed Tbx proteins could be a common theme across developmental processes in cell lineages and tissues. Together, this work provides mechanistic insight into the role of TBX2 in human disorders affecting the face and neck.

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nkx2.3 expression.nkx2.3 is expressed in the segmented endodermal pouches in control (A, C) and morphant embryos. These segmented endodermal pouches are almost fused in the morphants (B, D). The rag1-positive thymus, a derivative of the endodermal pouch (E) is absent in the morphant (F). A: anterior, P: posterior.
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pone-0077171-g004: nkx2.3 expression.nkx2.3 is expressed in the segmented endodermal pouches in control (A, C) and morphant embryos. These segmented endodermal pouches are almost fused in the morphants (B, D). The rag1-positive thymus, a derivative of the endodermal pouch (E) is absent in the morphant (F). A: anterior, P: posterior.

Mentions: Although tbx2a expression was restricted to the endodermal compartment of the arches, its knock-down affected normal formation of the entire PA; this indicated the possible master role of tbx2a during PA development. To evaluate this possibility, we analyzed induction of the endodermal pouches between control and morphant embryos using nkx2.3, a specific marker of the endodermal pouch. nkx2.3 is expressed in the five domains between the six PAs [51]. In a ventral view, nkx2.3 revealed five pouches present in both the control and morphant embryos (Figure 4A, B), suggesting that induction of the endodermal pouches is not dependent on Tbx2a function. However, sagittal sections showed severely shortened nkx2.3 expression domains in the morphants as compared to controls (Figure 4C, D), suggesting a failure of the endodermal pouch to elongate and interdigitate with the NCC-derived compartment along the proximodistal axis. This correlates well with the tbx2a expression observed in the ventral aspect of the pouches. The thymus primordium appears in zebrafish larvae at 54 hpf as a derivative of the caudal half of endodermal pouch 3 [52]. In controls, we identified maturing B and T lymphocytes of the thymus from 96 hpf (Figure 3E) with positive rag1 staining [53]. However, in the morphants, the thymus was not detected (Figure 3F), further illustrating the endodermal pouch deficiency caused by down-regulation of tbx2a.


Tbx2a is required for specification of endodermal pouches during development of the pharyngeal arches.

Thi Thu HN, Haw Tien SF, Loh SL, Bok Yan JS, Korzh V - PLoS ONE (2013)

nkx2.3 expression.nkx2.3 is expressed in the segmented endodermal pouches in control (A, C) and morphant embryos. These segmented endodermal pouches are almost fused in the morphants (B, D). The rag1-positive thymus, a derivative of the endodermal pouch (E) is absent in the morphant (F). A: anterior, P: posterior.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3795029&req=5

pone-0077171-g004: nkx2.3 expression.nkx2.3 is expressed in the segmented endodermal pouches in control (A, C) and morphant embryos. These segmented endodermal pouches are almost fused in the morphants (B, D). The rag1-positive thymus, a derivative of the endodermal pouch (E) is absent in the morphant (F). A: anterior, P: posterior.
Mentions: Although tbx2a expression was restricted to the endodermal compartment of the arches, its knock-down affected normal formation of the entire PA; this indicated the possible master role of tbx2a during PA development. To evaluate this possibility, we analyzed induction of the endodermal pouches between control and morphant embryos using nkx2.3, a specific marker of the endodermal pouch. nkx2.3 is expressed in the five domains between the six PAs [51]. In a ventral view, nkx2.3 revealed five pouches present in both the control and morphant embryos (Figure 4A, B), suggesting that induction of the endodermal pouches is not dependent on Tbx2a function. However, sagittal sections showed severely shortened nkx2.3 expression domains in the morphants as compared to controls (Figure 4C, D), suggesting a failure of the endodermal pouch to elongate and interdigitate with the NCC-derived compartment along the proximodistal axis. This correlates well with the tbx2a expression observed in the ventral aspect of the pouches. The thymus primordium appears in zebrafish larvae at 54 hpf as a derivative of the caudal half of endodermal pouch 3 [52]. In controls, we identified maturing B and T lymphocytes of the thymus from 96 hpf (Figure 3E) with positive rag1 staining [53]. However, in the morphants, the thymus was not detected (Figure 3F), further illustrating the endodermal pouch deficiency caused by down-regulation of tbx2a.

Bottom Line: While tbx2a expression is restricted to the endodermal pouches, its function is required for the normal morphogenesis of the entire pharyngeal arches.The use of bimolecular fluorescence complementation revealed the interaction between Tbx2a and Tbx1, thus providing support for the idea that functional interaction between different, co-expressed Tbx proteins could be a common theme across developmental processes in cell lineages and tissues.Together, this work provides mechanistic insight into the role of TBX2 in human disorders affecting the face and neck.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular and Cell Biology, Singapore, Singapore ; Department of Biological Sciences, National University of Singapore, Singapore, Singapore ; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

ABSTRACT
Tbx2 is a member of the T-box family of transcription factors essential for embryo- and organogenesis. A deficiency in the zebrafish paralogue tbx2a causes abnormalities of the pharyngeal arches in a p53-independent manner. The pharyngeal arches are formed by derivatives of all three embryonic germ layers: endodermal pouches, mesenchymal condensations and neural crest cells. While tbx2a expression is restricted to the endodermal pouches, its function is required for the normal morphogenesis of the entire pharyngeal arches. Given the similar function of Tbx1 in craniofacial development, we explored the possibility of an interaction between Tbx1 and Tbx2a. The use of bimolecular fluorescence complementation revealed the interaction between Tbx2a and Tbx1, thus providing support for the idea that functional interaction between different, co-expressed Tbx proteins could be a common theme across developmental processes in cell lineages and tissues. Together, this work provides mechanistic insight into the role of TBX2 in human disorders affecting the face and neck.

Show MeSH
Related in: MedlinePlus