scholarly journals Regulatory integration of Hox factor activity with T-box factors in limb development

Development ◽  
2018 ◽  
Vol 145 (6) ◽  
pp. dev159830 ◽  
Author(s):  
Deepak Jain ◽  
Stephen Nemec ◽  
Maëva Luxey ◽  
Yves Gauthier ◽  
Amandine Bemmo ◽  
...  
Keyword(s):  
Limb Development ◽  
Factor Activity ◽  
T Box

scholarly journals MicroRNA-17-92, a Direct Ap-2α Transcriptional Target, Modulates T-Box Factor Activity in Orofacial Clefting

PLoS Genetics ◽  
2013 ◽  
Vol 9 (9) ◽  
pp. e1003785 ◽  
Author(s):  
Jun Wang ◽  
Yan Bai ◽  
Hong Li ◽  
Stephanie B. Greene ◽  
Elzbieta Klysik ◽  
...  
Keyword(s):  
Factor Activity ◽  
T Box ◽  
Orofacial Clefting ◽  
Transcriptional Target

scholarly journals Different Regulation of T-Box Genes Tbx4 and Tbx5 during Limb Development and Limb Regeneration

2002 ◽  
Vol 250 (2) ◽  
pp. 383-392 ◽  
Author(s):  
Paul Khan ◽  
Barbara Linkhart ◽  
Hans-Georg Simon
Keyword(s):  
Limb Development ◽  
Limb Regeneration ◽  
T Box

Involvement of T-box genes Tbx2-Tbx5 in vertebrate limb specification and development

Development ◽  
1998 ◽  
Vol 125 (13) ◽  
pp. 2499-2509 ◽  
Author(s):  
J.J. Gibson-Brown ◽  
S.I. Agulnik ◽  
L.M. Silver ◽  
L. Niswander ◽  
V.E. Papaioannou
Keyword(s):  
Gene Expression ◽  
Limb Development ◽  
T Box ◽  
Cell Pellet ◽  
Wing Bud ◽  
Zone Of Polarizing Activity ◽  
The Relationship ◽  
Tbx2 Expression ◽  
Limb Specification

We have recently shown in mice that four members of the T-box family of transcription factors (Tbx2-Tbx5) are expressed in developing limb buds, and that expression of two of these genes, Tbx4 and Tbx5, is primarily restricted to the developing hindlimbs and forelimbs, respectively. In this report, we investigate the role of these genes in limb specification and development, using the chick as a model system. We induced the formation of ectopic limbs in the flank of chick embryos to examine the relationship between the identity of the limb-specific T-box genes being expressed and the identity of limb structures that subsequently develop. We found that, whereas bud regions expressing Tbx4 developed characteristic leg structures, regions expressing Tbx5 developed characteristic wing features. In addition, heterotopic grafts of limb mesenchyme (wing bud into leg bud, and vice versa), which are known to retain the identity of the donor tissue after transplantation, retained autonomous expression of the appropriate, limb-specific T-box gene, with no evidence of regulation by the host bud. Thus there is a direct relationship between the identity of the structures that develop in normal, ectopic and recombinant limbs, and the identity of the T-box gene(s) being expressed. To investigate the regulation of T-box gene expression during limb development, we employed several other embryological manipulations. By surgically removing the apical ectodermal ridge (AER) from either wing or leg buds, we found that, in contrast to all other genes implicated in the patterning of developing appendages, maintenance of T-box gene expression is not dependent on the continued provision of signals from the AER or the zone of polarizing activity (ZPA). By generating an ectopic ZPA, by grafting a sonic hedgehog (SHH)-expressing cell pellet under the anterior AER, we found that Tbx2 expression can lie downstream of SHH. Finally, by grafting a SHH-expressing cell pellet to the anterior margin of a bud from which the AER had been removed, we found that Tbx2 may be a direct, short-range target of SHH. Our findings suggest that these genes are intimately involved in limb development and the specification of limb identity, and a new model for the evolution of vertebrate appendages is proposed.

The limb identity gene Tbx5 promotes limb initiation by interacting with Wnt2b and Fgf10

Development ◽  
2002 ◽  
Vol 129 (22) ◽  
pp. 5161-5170 ◽  
Author(s):  
Jennifer K. Ng ◽  
Yasuhiko Kawakami ◽  
Dirk Büscher ◽  
Ángel Raya ◽  
Tohru Itoh ◽  
...  
Keyword(s):  
Limb Development ◽  
Gene Families ◽  
Chick Embryos ◽  
Loss Of Function ◽  
T Box ◽  
Vertebrate Limb ◽  
Limb Outgrowth ◽  
Tbx5 Expression ◽  
Necessary And Sufficient ◽  
Limb Initiation

A major gap in our knowledge of development is how the growth and identity of tissues and organs are linked during embryogenesis. The vertebrate limb is one of the best models to study these processes. Combining mutant analyses with gain- and loss-of-function approaches in zebrafish and chick embryos, we show that Tbx5, in addition to its role governing forelimb identity,is both necessary and sufficient for limb outgrowth. We find thatTbx5 functions downstream of WNT signaling to regulateFgf10, which, in turn, maintains Tbx5 expression during limb outgrowth. Furthermore, our results indicate that Tbx5 andWnt2b function together to initiate and specify forelimb outgrowth and identity. The molecular interactions governed by members of the T-box,Wnt and Fgf gene families uncovered in this study provide a framework for understanding not only limb development, but how outgrowth and identity of other tissues and organs of the embryo may be regulated.

scholarly journals HDAC4 and 5 repression of TBX5 is relieved by protein kinase D1

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Tushar K. Ghosh ◽  
José J. Aparicio-Sánchez ◽  
Sarah Buxton ◽  
J. David Brook
Keyword(s):  
Transcription Factor ◽  
Protein Kinase ◽  
Gene Transcription ◽  
Histone Deacetylases ◽  
Limb Development ◽  
Transcriptional Activity ◽  
Class Ii ◽  
T Box ◽  
Protein Kinase D1 ◽  
Cardiac Gene

AbstractTBX5 is a T-box family transcription factor that regulates heart and forelimb development in vertebrates and functional deficiencies in this protein result in Holt-Oram syndrome. Recently, we have shown that acetylation of TBX5 potentiates its activity and is important for heart and limb development. Here we report that class II histone deacetylases HDAC4 and HDAC5 associate with TBX5 and repress its role in cardiac gene transcription. Both HDAC4 and HDAC5 deacetylate TBX5, which promotes its relocation to the cytoplasm and HDAC4 antagonizes the physical association and functional cooperation between TBX5 and MEF2C. We also show that protein kinase D1 (PRKD1) relieves the HDAC4/5-mediated repression of TBX5. Thus, this study reveals a novel interaction of HDAC4/5 and PRKD1 in the regulation of TBX5 transcriptional activity.

scholarly journals T-box3 is a ciliary protein and regulates stability of the Gli3 transcription factor to control digit number

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Uchenna Emechebe ◽  
Pavan Kumar P ◽  
Julian M Rozenberg ◽  
Bryn Moore ◽  
Ashley Firment ◽  
...  
Keyword(s):  
Limb Development ◽  
Primary Cilia ◽  
Digit Number ◽  
Posterior Limb ◽  
T Box ◽  
Pathway Function ◽  
Mouse Limb ◽  
Limb Malformations ◽  
And Function ◽  
Tissue Compartments

Crucial roles for T-box3 in development are evident by severe limb malformations and other birth defects caused by T-box3 mutations in humans. Mechanisms whereby T-box3 regulates limb development are poorly understood. We discovered requirements for T-box at multiple stages of mouse limb development and distinct molecular functions in different tissue compartments. Early loss of T-box3 disrupts limb initiation, causing limb defects that phenocopy Sonic Hedgehog (Shh) mutants. Later ablation of T-box3 in posterior limb mesenchyme causes digit loss. In contrast, loss of anterior T-box3 results in preaxial polydactyly, as seen with dysfunction of primary cilia or Gli3-repressor. Remarkably, T-box3 is present in primary cilia where it colocalizes with Gli3. T-box3 interacts with Kif7 and is required for normal stoichiometry and function of a Kif7/Sufu complex that regulates Gli3 stability and processing. Thus, T-box3 controls digit number upstream of Shh-dependent (posterior mesenchyme) and Shh-independent, cilium-based (anterior mesenchyme) Hedgehog pathway function.

A novel family of T-box genes in urodele amphibian limb development and regeneration: candidate genes involved in vertebrate forelimb/hindlimb patterning

Development ◽  
1997 ◽  
Vol 124 (7) ◽  
pp. 1355-1366 ◽  
Author(s):  
H.G. Simon ◽  
R. Kittappa ◽  
P.A. Khan ◽  
C. Tsilfidis ◽  
R.A. Liversage ◽  
...  
Keyword(s):  
Limb Development ◽  
Expression Patterns ◽  
Mrna Differential Display ◽  
Limb Bud ◽  
Morphological Pattern ◽  
Epimorphic Regeneration ◽  
T Box ◽  
Evolutionarily Conserved ◽  
T Domain

In certain urodeles, a lost appendage, including hand and foot, can be completely replaced through epimorphic regeneration. The regeneration process involves cellular activities similar to those described for embryogenesis. Working on the assumption that the morphological pattern specific for a forelimb or a hindlimb is controlled by different gene activities in the two limbs, we employed a mRNA differential display screen for the detection of candidate limb identity genes. Using this approach, we have isolated a newt gene which in regenerating and developing limbs reveals properties expected of a gene having a role in controlling limb morphology: (1) it is exclusively expressed in the forelimbs, but not hindlimbs, (2) during embryonic development its expression is co-incident with forelimb bud formation, (3) it has an elevated message level throughout the undifferentiated limb bud and the blastema, respectively, and (4) it is expressed only in mesenchymal, but not in epidermal tissues. This novel newt gene shares a conserved DNA-binding domain, the T-box, with putative transcription factors including the Brachyury (T) gene product. In a following PCR-based screen, we used the evolutionarily conserved T-box motif and amplified a family of related genes in the newt; their different expression patterns in normal and regenerating forelimbs, hindlimbs and tail suggest, in general, an important role of T-domain proteins in vertebrate pattern formation.

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