Hox-4 gene expression in mouse/chicken heterospecific grafts of signalling regions to limb buds reveals similarities in patterning mechanisms

Development ◽  
1992 ◽  
Vol 115 (2) ◽  
pp. 553-560 ◽  
Author(s):  
J.C. Izpisua-Belmonte ◽  
J.M. Brown ◽  
A. Crawley ◽  
D. Duboule ◽  
C. Tickle
Keyword(s):  
Gene Expression ◽  
Gene Network ◽  
Primitive Streak ◽  
Mouse Embryos ◽  
Limb Bud ◽  
Chick Embryos ◽  
Mouse Limb ◽  
Mouse Cells ◽  
Species Specific ◽  
Genital Tubercle

The products of Hox-4 genes appear to encode position in developing vertebrate limbs. In chick embryos, a number of different signalling regions when grafted to wing buds lead to duplicated digit patterns. We grafted tissue from the equivalent regions in mouse embryos to chick wing buds and assayed expression of Hox-4 genes in both the mouse cells in the grafts and in the chick cells in the responding limb bud using species specific probes. Tissue from the mouse limb polarizing region and anterior primitive streak respecify anterior chick limb bud cells to give posterior structures and lead to activation of all the genes in the complex. Mouse neural tube and genital tubercle grafts, which give much less extensive changes in pattern, do not activate 5′-located Hox-4 genes. Analysis of expression of Hox-4 genes in mouse cells in the grafted signalling regions reveals no relationship between expression of these genes and strength of their signalling activity. Endogenous signals in the chick limb bud activate Hox-4 genes in grafts of mouse anterior limb cells when placed posteriorly and in grafts of mouse anterior primitive streak tissue. The activation of the same gene network by different signalling regions points to a similarity in patterning mechanisms along the axes of the vertebrate body.

Ultrastructural aspects of early development of the fore-limb buds in the chick and the mouse

1965 ◽  
Vol 162 (988) ◽  
pp. 387-405 ◽  
Keyword(s):  
Endoplasmic Reticulum ◽  
Early Development ◽  
Secretory Granules ◽  
Free Cell ◽  
Mouse Embryos ◽  
Limb Bud ◽  
Chick Embryos ◽  
Limb Buds ◽  
Mouse Limb ◽  
A Chain

Light microscope investigations of the early development of the fore-limb buds in chick and mouse were made to guide electron microscope studies with these tissues. At the time of maximal development of the ectodermal apical ridge there is a higher concentration of cytoplasmic RNA in the apical ridge cells than in the other cells of the limb bud. Ultrastructural investigations showed that, in the mesoblast cells at the earliest stages, profiles of endoplasmic reticulum are often found attached to the outer nuclear membrane. Some what later, discontinuities of nuclear envelope occur by which the content of the nucleus may communicate with the endoplasmic reticulum. In the cytoplasm of the mesoblast cells at these stages there were many granules similar in form and size to secretory granules of gland cells. Ribosomes are in the polysomal condition. At stages later than 20 in chick and in 11-day-old mouse embryos, the mesoblast shows the character of a syncytial tissue. Epiblast cells possess all the characters of an epithelium with well developed junctional complexes. The desmosomes form a chain consisting of units equipped with individual dense plaques, but connected by continuous bundles of fibres running parallel to the chain. The free cell membrane of the epiblastic cells, particularly at early stages, forms numerous microvilli and single cilia. In later stages during the form action of the ectodermal apical ridge, cilia have been found between the cells. This fact indicates that when the apical ridge is formed ectodermal cells migrate towards the margin of the limb bud. At these stages microvilli are also found between the apical ridge cells where they contribute to the cell-to-cell adhesion. Beginning at stage 22 in chick embryos and from the 12th day in mouse embryos there are in cells of the apical ridge numerous and extensive Golgi systems spread throughout the cytoplasm. Some what later there appear successively lysosomes, cytolysomes and extranuclear necrotic centres. All these organelles manifest acid phosphatase activity and are thoughtto initiate the involutive process in the apical ridge. Pycnosis and karyorrhexis appear as the last stage of cellular degeneration. Degenerating cells undergo phagocytosis by neighbouring epithelial cells. A basement membrane is present at all stages of development of the chick and mouse limb buds. It is an acellular continuous structure lining the internal (basal) surface of the epiblast, but in chick embryos it shows discontinuities immediately under the apical ectodermal ridge at the time of its maximum development.

scholarly journals SMAD4 target genes are part of a transcriptional network that integrates the response to BMP and SHH signaling during early limb bud patterning

Development ◽  
2021 ◽  
Author(s):  
Julie Gamart ◽  
Iros Barozzi ◽  
Frédéric Laurent ◽  
Robert Reinhardt ◽  
Laurène Ramos Martins ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Target Genes ◽  
Cholesterol Biosynthesis ◽  
Limb Bud ◽  
Limb Buds ◽  
Shh Signaling ◽  
Mesenchymal Progenitors ◽  
Repressive Effect ◽  
Mouse Limb

SMAD4 regulates gene expression in response to BMP and TGFβ signal transduction and is required for diverse morphogenetic processes, but its target genes have remained largely elusive. Here, we identify the SMAD4 target genes in mouse limb buds using an epitope-tagged Smad4 allele for ChIP-seq analysis in combination with transcription profiling. This analysis shows that SMAD4 predominantly mediates BMP signal-transduction during early limb bud development. Unexpectedly, the expression of cholesterol biosynthesis enzymes is precociously down-regulated and intracellular cholesterol levels are reduced in Smad4-deficient limb bud mesenchymal progenitors. Most importantly, our analysis reveals a predominant function of SMAD4 in up-regulating target genes in the anterior limb bud mesenchyme. Analysis of differentially expressed genes shared between Smad4- and Shh-deficient limb buds corroborates this function of SMAD4 and also reveals the repressive effect of SMAD4 on posterior genes that are up-regulated in response to SHH signaling. This analysis uncovers opposing trans-regulatory inputs from SHH and SMAD4-mediated BMP signal transduction on anterior and posterior gene expression during the digit patterning and outgrowth in early limb buds.

The chick limbless mutation causes abnormalities in limb bud dorsal-ventral patterning: implications for the mechanism of apical ridge formation

Development ◽  
1996 ◽  
Vol 122 (12) ◽  
pp. 3851-3861 ◽  
Author(s):  
U. Grieshammer ◽  
G. Minowada ◽  
J.M. Pisenti ◽  
U.K. Abbott ◽  
G.R. Martin
Keyword(s):  
Gene Expression ◽  
Limb Development ◽  
Positional Information ◽  
Limb Bud ◽  
Local Application ◽  
Chick Embryos ◽  
Limb Buds ◽  
Early Stages ◽  
Potential Link

In chick embryos homozygous for the limbless mutation, limb bud outgrowth is initiated, but a morphologically distinct apical ridge does not develop and limbs do not form. Here we report the results of an analysis of gene expression in limbless mutant limb buds. Fgf4, Fgf8, Bmp2 and Msx2, genes that are expressed in the apical ridge of normal limb buds, are not expressed in the mutant limb bud ectoderm, providing molecular support for the hypothesis that limb development fails in the limbless embryo because of the inability of the ectoderm to form a functional ridge. Moreover, Fgf8 expression is not detected in the ectoderm of the prospective limb territory or the early limb bud of limbless embryos. Since the early stages of limb bud outgrowth occur normally in the mutant embryos, this indicates that FGF8 is not required to promote initial limb bud outgrowth. In the absence of FGF8, Shh is also not expressed in the mutant limb buds, although its expression can be induced by application of FGF8-soaked beads. These observations support the hypothesis that Fgf8 is required for the induction of Shh expression during normal limb development. Bmp2 expression was also not detected in mutant limb mesoderm, consistent with the hypothesis that SHH induces its expression. In contrast, SHH is not required for the induction of Hoxd11 or Hoxd13 expression, since expression of both these genes was detected in the mutant limb buds. Thus, some aspects of mesoderm A-P patterning can occur in the absence of SHH and factors normally expressed in the apical ridge. Intriguingly, mutant limbs rescued by local application of FGF displayed a dorsalized feather pattern. Furthermore, the expression of Wnt7a, Lmx1 and En1, genes involved in limb D-V patterning, was found to be abnormal in mutant limb buds. These data suggest that D-V patterning and apical ridge formation are linked, since they show that the limbless mutation affects both processes. We present a model that explains the potential link between D-V positional information and apical ridge formation, and discuss the possible function of the limbless gene in terms of this model.

Homoeobox gene expression in mouse embryos varies with position by the primitive streak stage

Nature ◽  
1986 ◽  
Vol 324 (6098) ◽  
pp. 662-664 ◽  
Author(s):  
Stephen J. Gaunt ◽  
J. Ross Miller ◽  
Donald J. Powell ◽  
Denis Duboule
Keyword(s):  
Gene Expression ◽  
Primitive Streak ◽  
Mouse Embryos

scholarly journals Conserved and species-specific chromatin remodeling and regulatory dynamics during mouse and chicken limb bud development

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shalu Jhanwar ◽  
Jonas Malkmus ◽  
Jens Stolte ◽  
Olga Romashkina ◽  
Aimée Zuniga ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Chromatin Remodeling ◽  
Limb Development ◽  
Gene Networks ◽  
Temporal Dynamics ◽  
Regulation Of Gene Expression ◽  
Limb Bud ◽  
Species Specific ◽  
The Impact

AbstractChromatin remodeling and genomic alterations impact spatio-temporal regulation of gene expression, which is central to embryonic development. The analysis of mouse and chicken limb development provides important insights into the morphoregulatory mechanisms, however little is known about the regulatory differences underlying their morphological divergence. Here, we identify the underlying shared and species-specific epigenomic and genomic variations. In mouse forelimb buds, we observe striking synchrony between the temporal dynamics of chromatin accessibility and gene expression, while their divergence in chicken wing buds uncovers species-specific regulatory heterochrony. In silico mapping of transcription factor binding sites and computational footprinting establishes the developmental time-restricted transcription factor-DNA interactions. Finally, the construction of target gene networks for HAND2 and GLI3 transcriptional regulators reveals both conserved and species-specific interactions. Our analysis reveals the impact of genome evolution on the regulatory interactions orchestrating vertebrate limb bud morphogenesis and provides a molecular framework for comparative Evo-Devo studies.

scholarly journals Manipulating gene expression and signaling activity in cultured mouse limb bud cells

2014 ◽  
Vol 243 (7) ◽  
pp. 928-936 ◽  
Author(s):  
Jordan P. Lewandowski ◽  
Taylor A. Pursell ◽  
Adam H. Rabinowitz ◽  
Steven A. Vokes
Keyword(s):  
Gene Expression ◽  
Limb Bud ◽  
Mouse Limb ◽  
Signaling Activity

scholarly journals Induction of immunoglobulin gene expression in mouse fibroblasts by cycloheximide treatment.

1984 ◽  
Vol 160 (6) ◽  
pp. 1937-1942 ◽  
Author(s):  
T Ishihara ◽  
A Kudo ◽  
T Watanabe
Keyword(s):  
Gene Expression ◽  
Chain Gene ◽  
Immunoglobulin Gene ◽  
L Cells ◽  
Short Period ◽  
Mouse Cells ◽  
Complete Set ◽  
Repressor Molecule ◽  
Species Specific

A complete set of a rearranged human gamma 1-heavy chain gene, HIG1, was cloned from human plasma cell leukemia line, ARH-77, and transferred into mouse cells. It was strongly expressed in mouse myeloma cells but not in mouse L cells, indicating that immunoglobulin gene expression is not species-specific but cell-specific. However, a remarkable production of human gamma 1 chain was induced in mouse L cells containing HIG1 gene when the cells were treated with cycloheximide for a short period. The role of a labile repressor molecule in the expression of the immunoglobulin gene is proposed.

The origin and movements of the hepatogenic cells in the chick embryo as determined by radioautographic mapping

Development ◽  
1971 ◽  
Vol 25 (1) ◽  
pp. 97-113
Author(s):  
Glenn C. Rosenquist
Keyword(s):  
Chick Embryo ◽  
Developmental Stage ◽  
Primitive Streak ◽  
Limb Bud ◽  
Chick Embryos ◽  
Lateral Plate Mesoderm ◽  
Lateral Plate ◽  
Somite Stage ◽  
Definition Of ◽  
Exact Definition

The origin of the prehepatic cells was determined by tracing the movements of [3H]thymidine-labelled grafts excised from medium-streak to 4-somite stage chick embryos and transplanted to the epiblast, streak and endoderm-mesoderm layer of similarly staged recipient embryos. Although exact definition of prehepatic areas was not possible because of the small number of grafts placed at each developmental stage, the study showed in general that at the medium-streak stage, the prehepatic endoderm cells are in the anterior third of the primitive streak; they shortly begin to migrate anteriorly and laterally into the endoderm layer ventral to the precardiac areas of mesoderm. They are in the yolk-sac endoderm at the 2–4-somite stage, and by the 15–17-somite stage are clustered at the anterior intestinal portal. At the 26-somite to early limb-bud stages, the anterior and posterior liver diverticula have formed from these endoderm cells, and some of the branches of the diverticula may have reached the prehepatic mesenchyme, where the two tissues have begun to form cords and sinuses. At the medium-streak stage, the prehepatic mesoderm is located slightly more than halfway from the anterior to the posterior end of the primitive streak. From this position it migrates anteriorly and laterally into the lateral plate mesoderm, and from the head-process to the 2–4-somite stage it is situated posterior to the prehepatic endoderm and posterior and lateral to the heart-forming portion of the splanchnic layer. By the 15–17-somite stage the prehepatic mesoderm has reached a position in the splanchnic layer of mesoderm which forms the dorsolateral wall of the sinus venosus. By the 26-somite to early limb-bud stage the hepatic diverticula have joined with the hepatic mesenchyme to form the rudimentary cords and sinuses of the liver.

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.

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