scholarly journals Proximo-distal positional information encoded by an Fgf-regulated gradient of homeodomain transcription factors in the vertebrate limb

2020 ◽  
Vol 6 (23) ◽  
pp. eaaz0742 ◽  
Author(s):  
Irene Delgado ◽  
Alejandra C. López-Delgado ◽  
Alberto Roselló-Díez ◽  
Giovanna Giovinazzo ◽  
Vanessa Cadenas ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Molecular Basis ◽  
Positional Information ◽  
Limb Bud ◽  
Embryonic Cells ◽  
Axial Patterning ◽  
Vertebrate Limb ◽  
Mouse Limb ◽  
Position And Orientation ◽  
Homeodomain Transcription Factors

The positional information theory proposes that a coordinate system provides information to embryonic cells about their position and orientation along a patterning axis. Cells interpret this information to produce the appropriate pattern. During development, morphogens and interpreter transcription factors provide this information. We report a gradient of Meis homeodomain transcription factors along the mouse limb bud proximo-distal (PD) axis antiparallel to and shaped by the inhibitory action of distal fibroblast growth factor (FGF). Elimination of Meis results in premature limb distalization and HoxA expression, proximalization of PD segmental borders, and phocomelia. Our results show that Meis transcription factors interpret FGF signaling to convey positional information along the limb bud PD axis. These findings establish a new model for the generation of PD identities in the vertebrate limb and provide a molecular basis for the interpretation of FGF signal gradients during axial patterning.

scholarly journals Analysis of transcription factors expressed at the anterior mouse limb bud

PLoS ONE ◽  
2017 ◽  
Vol 12 (5) ◽  
pp. e0175673 ◽  
Author(s):  
Shigetoshi Yokoyama ◽  
Soichi Furukawa ◽  
Shoya Kitada ◽  
Masaki Mori ◽  
Takeshi Saito ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Limb Bud ◽  
Mouse Limb

Maintenance of ZPA signaling in cultured mouse limb bud cells

Development ◽  
1993 ◽  
Vol 117 (4) ◽  
pp. 1421-1433 ◽  
Author(s):  
R. Anderson ◽  
M. Landry ◽  
K. Muneoka
Keyword(s):  
Culture Technique ◽  
Limb Bud ◽  
In Vivo Studies ◽  
Maintenance Activity ◽  
Vertebrate Limb ◽  
Mouse Limb ◽  
Zone Of Polarizing Activity

The positional signal localized to the posterior (zone of polarizing activity or ZPA) region of the vertebrate limb is transiently expressed during development and a decline in ZPA signaling is accelerated when posterior cells are dissociated and cultured in vitro. The evidence that cultured posterior cells display a precocious decline in ZPA signaling when compared to in vivo studies suggests that a factor present in the limb bud maintains or stabilizes ZPA signaling during limb outgrowth and that this maintenance factor is lost and/or exhausted in in vitro studies. We have developed a new culture technique, ‘microdissociation’, which preserves extracellular components that we have found to be necessary for ZPA signal maintenance. Our data suggest that the limb bud ectoderm produces a maintenance activity that becomes stored in the extracellular matrix where it acts on limb bud cells to stabilize the activity of the ZPA signal. Using our initial characterization of this maintenance activity, we have identified a growth factor, FGF-2 (bFGF), that can replace all of the ZPA signaling maintenance activity observed in microdissociate cultures. The existence of various members of the FGF family in the developing limb strongly argues a role for FGF in stabilizing ZPA signaling in vivo.

scholarly journals Pattern formation in epithelial development: the vertebrate limb and feather bud spacing

1998 ◽  
Vol 353 (1370) ◽  
pp. 871-875 ◽  
Author(s):  
Lewis Wolpert
Keyword(s):  
Growth Factors ◽  
Imaginal Disc ◽  
Fibroblast Growth Factors ◽  
Limb Bud ◽  
Fibroblast Growth ◽  
Vertebrate Development ◽  
Epithelial Development ◽  
Vertebrate Limb ◽  
Mouse Limb ◽  
Dorsal Cells

The ectoderm of the vertebrate limb and feather bud are epithelia that provide good models for epithelial patterning in vertebrate development. At the tip of chick and mouse limb buds is a thickening, the apical ectodermal ridge, which is essential for limb bud outgrowth. The signal from the ridge to the underlying mesoderm involves fibroblast growth factors. The non–ridge ectoderm specifies the dorsoventral pattern of the bud and Wnt7a is a dorsalizing signal. The development of the ridge involves an interaction between dorsal cells that express radical fringe and those that do not. There are striking similarities between the signals and genes involved in patterning the limb ectoderm and the epithelia of the Drosophila imaginal disc that gives rise to the wing. The spacing of feather buds involves signals from the epidermis to the underlying mesenchyme, which again include Wnt7a and fibroblast growth factors.

scholarly journals Geminin is required for Hox gene regulation to pattern the developing limb

2020 ◽  
Author(s):  
Emily M.A. Lewis ◽  
Savita Sankar ◽  
Caili Tong ◽  
Ethan Patterson ◽  
Laura E. Waller ◽  
...  
Keyword(s):  
Gene Expression ◽  
Limb Development ◽  
Complex Structure ◽  
Limb Bud ◽  
Conditional Model ◽  
Regulatory Pathways ◽  
Shh Pathway ◽  
Severe Reduction ◽  
Vertebrate Limb ◽  
Mouse Limb

AbstractDevelopment of the complex structure of the vertebrate limb requires carefully orchestrated interactions between multiple regulatory pathways and proteins. Among these, precise regulation of 5’ Hox transcription factor expression is essential for proper limb bud patterning and elaboration of distinct limb skeletal elements. Here, we identified Geminin (Gmnn) as a novel regulator of this process. A conditional model of Gmnn deficiency resulted in loss or severe reduction of forelimb skeletal elements, while both the forelimb autopod and hindlimb were unaffected. 5’ Hox gene expression expanded into more proximal and anterior regions of the embryonic forelimb buds in this Gmnn-deficient model. A second conditional model of Gmnn deficiency instead caused a similar but less severe reduction of hindlimb skeletal elements and hindlimb polydactyly, while not affecting the forelimb. An ectopic posterior SHH signaling center was evident in the anterior hindlimb bud of Gmnn-deficient embryos in this model. This center ectopically expressed Hoxd13, the HOXD13 target Shh, and the SHH target Ptch1, while these mutant hindlimb buds also had reduced levels of the cleaved, repressor form of GLI3, a SHH pathway antagonist. Together, this work delineates a new role for Gmnn in modulating Hox expression to pattern the vertebrate limb.SummaryThis work identifies a new role for Geminin in mouse limb development. Geminin is a nuclear protein that regulates gene expression to control several other aspects of vertebrate development.

Misexpression of Sox9 in mouse limb bud mesenchyme induces polydactyly and rescues hypodactyly mice

2007 ◽  
Vol 26 (4) ◽  
pp. 224-233 ◽  
Author(s):  
Haruhiko Akiyama ◽  
H. Scott Stadler ◽  
James F. Martin ◽  
Takahiro M. Ishii ◽  
Philip A. Beachy ◽  
...  
Keyword(s):  
Limb Bud ◽  
Mouse Limb

FGF-4 maintains polarizing activity of posterior limb bud cells in vivo and in vitro

Development ◽  
1993 ◽  
Vol 119 (1) ◽  
pp. 199-206 ◽  
Author(s):  
A. Vogel ◽  
C. Tickle
Keyword(s):  
Posterior Margin ◽  
Anterior Margin ◽  
Marked Decrease ◽  
Mesenchymal Cells ◽  
Apical Ectodermal Ridge ◽  
Limb Bud ◽  
Posterior Limb ◽  
Vertebrate Limb

The polarizing region is a major signalling tissue involved in patterning the tissues of the vertebrate limb. The polarizing region is located at the posterior margin of the limb bud and can be recognized by its ability to induce additional digits when grafted to the anterior margin of a chick limb bud. The signal from the polarizing region operates at the tip of the bud in the progress zone, a zone of undifferentiated mesenchymal cells, maintained by interactions with the apical ectodermal ridge. A number of observations have pointed to a link between the apical ectodermal ridge and signalling by the polarizing region. To test this possibility, we removed the posterior apical ectodermal ridge of chick wing buds and assayed posterior mesenchyme for polarizing activity. When the apical ectodermal ridge is removed, there is a marked decrease in polarizing activity of posterior cells. The posterior apical ectodermal ridge is known to express FGF-4 and we show that the decrease in polarizing activity of posterior cells of wing buds that normally follows ridge removal can be prevented by implanting a FGF-4-soaked bead. Furthermore, we show that both ectoderm and FGF-4 maintain polarizing activity of limb bud cells in culture.

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