scholarly journals Establishing the pattern of the vertebrate limb

Development ◽  
2020 ◽  
Vol 147 (17) ◽  
pp. dev177956 ◽  
Author(s):  
Caitlin McQueen ◽  
Matthew Towers
Keyword(s):  
Gene Expression ◽  
Pattern Formation ◽  
Limb Bud ◽  
Complex Pattern ◽  
Digit Number ◽  
Vertebrate Limb ◽  
Undifferentiated Cells

ABSTRACTThe vertebrate limb continues to serve as an influential model of growth, morphogenesis and pattern formation. With this Review, we aim to give an up-to-date picture of how a population of undifferentiated cells develops into the complex pattern of the limb. Focussing largely on mouse and chick studies, we concentrate on the positioning of the limbs, the formation of the limb bud, the establishment of the principal limb axes, the specification of pattern, the integration of pattern formation with growth and the determination of digit number. We also discuss the important, but little understood, topic of how gene expression is interpreted into morphology.

The dominant hemimelia mutation uncouples epithelial-mesenchymal interactions and disrupts anterior mesenchyme formation in mouse hindlimbs

Development ◽  
1999 ◽  
Vol 126 (21) ◽  
pp. 4729-4736
Author(s):  
L. Lettice ◽  
J. Hecksher-Sorensen ◽  
R.E. Hill
Keyword(s):  
Gene Expression ◽  
Pattern Formation ◽  
Limb Development ◽  
Limb Bud ◽  
Mouse Mutation ◽  
Number Of Factors ◽  
Limb Outgrowth ◽  
Gene Functions ◽  
Regulatory Loop ◽  
Limb Initiation

Epithelial-mesenchymal interactions are essential for both limb outgrowth and pattern formation in the limb. Molecules capable of communication between these two tissues are known and include the signaling molecules SHH and FGF4, FGF8 and FGF10. Evidence suggests that the pattern and maintenance of expression of these genes are dependent on a number of factors including regulatory loops between genes expressed in the AER and those in the underlying mesenchyme. We show here that the mouse mutation dominant hemimelia (Dh) alters the pattern of gene expression in the AER such that Fgf4, which is normally expressed in a posterior domain, and Fgf8, which is expressed throughout are expressed in anterior patterns. We show that maintenance of Shh expression in the posterior mesenchyme is not dependent on either expression of Fgf4 or normal levels of Fgf8 in the overlying AER. Conversely, AER expression of Fgf4 is not directly dependent on Shh expression. Also the reciprocal regulatory loop proposed for Fgf8 in the AER and Fgf10 in the underlying mesenchyme is also uncoupled by this mutation. Early during the process of limb initiation, Dh is involved in regulating the width of the limb bud, the mutation resulting in selective loss of anterior mesenchyme. The Dh gene functions in the initial stages of limb development and we suggest that these initial roles are linked to mechanisms that pattern gene expression in the AER.

scholarly journals Fibroblast growth factor-induced gene expression and cartilage pattern formation in chick limb bud recombinants

2001 ◽  
Vol 43 (2) ◽  
pp. 165-175 ◽  
Author(s):  
Eiji Akiba ◽  
Sayuri Yonei-Tamura ◽  
Hiroshi Yajima ◽  
Minoru Omi ◽  
Mikiko Tanaka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Pattern Formation ◽  
Fibroblast Growth Factor ◽  
Limb Bud ◽  
Fibroblast Growth ◽  
And Cartilage

scholarly journals Cell fate in the chick limb bud and relationship to gene expression

Development ◽  
1997 ◽  
Vol 124 (10) ◽  
pp. 1909-1918 ◽  
Author(s):  
N. Vargesson ◽  
J.D. Clarke ◽  
K. Vincent ◽  
C. Coles ◽  
L. Wolpert ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Posterior Margin ◽  
Cell Lineage ◽  
Limb Bud ◽  
Cell Populations ◽  
Apical Region ◽  
Vertebrate Limb ◽  
Wing Bud ◽  
The Relationship

We have produced detailed fate maps for mesenchyme and apical ridge of a stage 20 chick wing bud. The fate maps of the mesenchyme show that most of the wing arises from the posterior half of the bud. Subapical mesenchyme gives rise to digits. Cell populations beneath the ridge in the mid apical region fan out into the anterior tip of the handplate, while posterior cell populations extend right along the posterior margin. Subapical mesenchyme of the leg bud behaves similarly. The absence of anterior bending of posterior cell populations has implications when considering models of vertebrate limb evolution. The fatemaps of the apical ridge show that there is also a marked anterior expansion and cells that were in anterior apical ridge later become incorporated into non-ridge ectoderm along the margin of the bud. Mesenchyme and apical ridge do not expand in concert--the apical ridge extends more anteriorly. We used the fatemaps to investigate the relationship between cell lineage and elaboration of Hoxd-13 and Fgf-4 domains. Hoxd-13 and Fgf-4 are initially expressed posteriorly until about the mid-point of the early wing bud in mesenchyme and apical ridge respectively. Later in development, the genes come to be expressed throughout most of the handplate and apical ridge respectively. We found that at the proximal edge of the Hoxd-13 domain, cell populations stopped expressing the gene as development proceeded and found no evidence that the changes in extent of the domains were due to initiation of gene expression in anterior cells. Instead the changes in extent of expression fit with the fate maps and can be attributed to expansion and fanning out of cell populations initially expressing the genes.

The limb field mesoderm determines initial limb bud anteroposterior asymmetry and budding independent of sonic hedgehog or apical ectodermal gene expressions

Development ◽  
1996 ◽  
Vol 122 (8) ◽  
pp. 2319-2330 ◽  
Author(s):  
M.A. Ros ◽  
A. Lopez-Martinez ◽  
B.K. Simandl ◽  
C. Rodriguez ◽  
J.C. Izpisua Belmonte ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sonic Hedgehog ◽  
Limb Bud ◽  
Gene Expressions ◽  
Limb Buds ◽  
Limb Initiation ◽  
Anteroposterior Polarity ◽  
Initial Pattern ◽  
Do So

We have analyzed the pattern of expression of several genes implicated in limb initiation and outgrowth using limbless chicken embryos. We demonstrate that the expressions of the apical ridge associated genes, Fgf-8, Fgf-4, Bmp-2 and Bmp-4, are undetectable in limbless limb bud ectoderm; however, FGF2 protein is present in the limb bud ectoderm. Shh expression is undetectable in limbless limb bud mesoderm. Nevertheless, limbless limb bud mesoderm shows polarization manifested by the asymmetric expression of Hoxd-11, −12 and −13, Wnt-5a and Bmp-4 genes. The posterior limbless limb bud mesoderm, although not actually expressing Shh, is competent to express it if supplied with exogenous FGF or transplanted to a normal apical ridge environment, providing further evidence of mesodermal asymmetry. Exogenous FGF applied to limbless limb buds permits further growth and determination of recognizable skeletal elements, without the development of an apical ridge. However, the cells competent to express Shh do so at reduced levels; nevertheless, Bmp-2 is then rapidly expressed in the posterior limbless mesoderm. limbless limb buds appear as bi-dorsal structures, as the entire limb bud ectoderm expresses Wnt-7a, a marker for dorsal limb bud ectoderm; the ectoderm fails to express En-1, a marker of ventral ectoderm. As expected, C-Lmx1, which is downstream of Wnt-7a, is expressed in the entire limbless limb bud mesoderm. We conclude that anteroposterior polarity is established in the initial limb bud prior to Shh expression, apical ridge gene expression or dorsal-ventral asymmetry. We propose that the initial pattern of gene expressions in the emergent limb bud is established by axial influences on the limb field. These permit the bud to emerge with asymmetric gene expression before Shh and the apical ridge appear. We report that expression of Fgf-8 by the limb ectoderm is not required for the initiation of the limb bud. The gene expressions in the pre-ridge limb bud mesoderm, as in the limb bud itself, are unstable without stimulation from the apical ridge and the polarizing region (Shh) after budding is initiated. We propose that the defect in limbless limb buds is the lack of a dorsal-ventral interface in the limb bud ectoderm where the apical ridge induction signal would be received and an apical ridge formed. These observations provide evidence for the hypothesis that the dorsal-ventral ectoderm interface is a precondition for apical ridge formation.

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.

scholarly journals Evolution of Antennapedia-Class Homeobox Genes

Genetics ◽  
1996 ◽  
Vol 142 (1) ◽  
pp. 295-303 ◽  
Author(s):  
Jianzhi Zhang ◽  
Masatoshi Nei
Keyword(s):  
Gene Expression ◽  
Homeobox Genes ◽  
Amino Acid Sequences ◽  
Gene Arrangement ◽  
Gene Duplications ◽  
Group I ◽  
Group 3 ◽  
Group Ii ◽  
Anterior Posterior

Antennapedia (Antp)-class homeobox genes are involved in the determination of pattern formation along the anterior-posterior axis of the animal embryo. A phylogenetic analysis of Antp-class homeodomains of the nematode, Drosophila, amphioxus, mouse, and human indicates that the 13 cognate group genes of this gene family can be divided into two major groups, i.e., groups I and II. Group I genes can further be divided into subgroups A (cognate groups 1–2), B (cognate group 3), and C (cognate groups 4–8), and group II genes can be divided into subgroups D (cognate groups 9–10) and E (cognate groups 11–13), though this classification is somewhat ambiguous. Evolutionary distances among different amino acid sequences suggest that the divergence between group I and group II genes occurred ∼1000 million years (MY) ago, and the five different subgroups were formed by ∼600 MY ago, probably before the divergence of Pseudocoelomates (e.g., nematodes) and Coelomates (e.g., insects and chordates). Our results show that the genes that are phylogenetically close are also closely located in the chromosome, suggesting that the colinearity between the gene expression and gene arrangement was generated by successive tandem gene duplications and that the gene arrangement has been maintained by some sort of selection.

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