Homeotic transformation of the occipital bones of the skull by ectopic expression of a homeobox gene

Nature ◽  
1992 ◽  
Vol 359 (6398) ◽  
pp. 835-841 ◽  
Author(s):  
Thomas Lufkin ◽  
Manuel Mark ◽  
Charles P. Hart ◽  
Pascal Dollé ◽  
Marianne LeMeur ◽  
...  
Keyword(s):  
Ectopic Expression ◽  
Homeobox Gene ◽  
Homeotic Transformation

Ectopic expression of the maize kn1 gene phenocopies the Hooded mutant of barley

Development ◽  
1997 ◽  
Vol 124 (19) ◽  
pp. 3737-3745 ◽  
Author(s):  
R.E. Williams-Carrier ◽  
Y.S. Lie ◽  
S. Hake ◽  
P.G. Lemaux
Keyword(s):  
Expression Pattern ◽  
Posttranscriptional Regulation ◽  
Cellular Differentiation ◽  
Ectopic Expression ◽  
Homeobox Gene ◽  
Mrna Localization ◽  
Constitutive Promoter ◽  
Homeotic Transformation ◽  
Shoot Meristems

The homeobox gene, knotted1, (kn1) is expressed in shoot meristems and is required for maintaining indeterminacy and preventing cellular differentiation. Awns, extensions of the bract-like lemma found in all grass inflorescences, are normally determinate structures. We show that ectopic expression of kn1 in the barley awn is sufficient to direct the development of ectopic meristems, forming inflorescence-like structures. This homeotic transformation is similar to the phenotype produced by misexpression of the barley hvknox3 gene, associated with the dominant Hooded mutant (Muller, K. J., Romano, N., Gerstner, O., Garcia-Maroto, F., Pozzi, C., Salamini, F. and Rohde, W. (1995) Nature 374, 727–730). We suggest that the inverse polarity of the ectopic flowers seen in Hooded and transgenic kn1 plants results from the transformation of the awn into reiterative inflorescence axes. We observed that the protein and mRNA localization of the transgene, driven by a constitutive promoter, is similar to the expression pattern of hvknox3 in awns of Hooded mutants, suggesting posttranscriptional regulation.

Isolation and characterization of a downstream target of Pax6 in the mammalian retinal primordium

Development ◽  
2001 ◽  
Vol 128 (20) ◽  
pp. 3987-3994 ◽  
Author(s):  
Gilbert Bernier ◽  
Wolfgang Vukovich ◽  
Lorenz Neidhardt ◽  
Bernhard G. Herrmann ◽  
Peter Gruss
Keyword(s):  
Transcription Factor ◽  
Expression Pattern ◽  
Large Scale ◽  
Ectopic Expression ◽  
Signal Transduction Pathway ◽  
Homeobox Gene ◽  
Optic Vesicle ◽  
Altered Expression ◽  
Retina Development ◽  
Isolation And Characterization

The transcription factor Pax6 is required for eye morphogenesis in humans, mice and insects, and can induce ectopic eye formation in vertebrate and invertebrate organisms. Although the role of Pax6 has intensively been studied, only a limited number of genes have been identified that depend on Pax6 activity for their expression in the mammalian visual system. Using a large-scale in situ hybridization screen approach, we have identified a novel gene expressed in the mouse optic vesicle. This gene, Necab, encodes a putative cytoplasmic Ca2+-binding protein and coincides with Pax6 expression pattern in the neural ectoderm of the optic vesicle and in the forebrain pretectum. Remarkably, Necab expression is absent in both structures in Pax6 mutant embryos. By contrast, the optic vesicle-expressed homeobox genes Rx, Six3, Otx2 and Lhx2 do not exhibit an altered expression pattern. Using gain-of-function experiments, we show that Pax6 can induce ectopic expression of Necab, suggesting that Necab is a direct or indirect transcriptional target of Pax6. In addition, we have found that Necab misexpression can induce ectopic expression of the homeobox gene Chx10, a transcription factor implicated in retina development. Taken together, our results provide evidence that Necab is genetically downstream of Pax6 and that it is a part of a signal transduction pathway in retina development.

Requirements of Lim1, a Drosophila LIM-homeobox gene, for normal leg and antennal development

Development ◽  
2000 ◽  
Vol 127 (20) ◽  
pp. 4315-4323 ◽  
Author(s):  
T. Tsuji ◽  
A. Sato ◽  
I. Hiratani ◽  
M. Taira ◽  
K. Saigo ◽  
...  
Keyword(s):  
Ectopic Expression ◽  
Homeobox Genes ◽  
Homeobox Gene ◽  
Homeodomain Protein ◽  
Border Cells ◽  
Null Mutant ◽  
Tarsal Segment ◽  
Segment Boundary ◽  
Leg Development ◽  
Antagonistic Interactions

During Drosophila leg development, the distal-most compartment (pretarsus) and its immediate neighbour (tarsal segment 5) are specified by a pretarsus-specific homeobox gene, aristaless, and tarsal-segment-specific Bar homeobox genes, respectively; the pretarsus/tarsal-segment boundary is formed by antagonistic interactions between Bar and pretarsus-specific genes that include aristaless (Kojima, T., Sato, M. and Saigo, K. (2000) Development 127, 769–778). Here, we show that Drosophila Lim1, a homologue of vertebrate Lim1 encoding a LIM-homeodomain protein, is involved in pretarsus specification and boundary formation through its activation of aristaless. Ectopic expression of Lim1 caused aristaless misexpression, while aristaless expression was significantly reduced in Lim1-null mutant clones. Pretarsus Lim1 expression was negatively regulated by Bar and abolished in leg discs lacking aristaless activity, which was associated with strong Bar misexpression in the presumptive pretarsus. No Lim1 misexpression occurred upon aristaless misexpression. The concerted function of Lim1 and aristaless was required to maintain Fasciclin 2 expression in border cells and form a smooth pretarsus/tarsal-segment boundary. Lim1 was also required for femur, coxa and antennal development.

A role for the vegetally expressed Xenopus gene Mix.1 in endoderm formation and in the restriction of mesoderm to the marginal zone

Development ◽  
1998 ◽  
Vol 125 (13) ◽  
pp. 2371-2380 ◽  
Author(s):  
P. Lemaire ◽  
S. Darras ◽  
D. Caillol ◽  
L. Kodjabachian
Keyword(s):  
Marginal Zone ◽  
Ectopic Expression ◽  
Homeobox Gene ◽  
Early Response ◽  
Endoderm Differentiation ◽  
Head Formation ◽  
Mutual Repression ◽  
Regulatory Loop ◽  
Strong Activator

We have studied the role of the activin immediate-early response gene Mix.1 in mesoderm and endoderm formation. In early gastrulae, Mix.1 is expressed throughout the vegetal hemisphere, including marginal-zone cells expressing the trunk mesodermal marker Xbra. During gastrulation, the expression domains of Xbra and Mix.1 become progressively exclusive as a result of the establishment of a negative regulatory loop between these two genes. This mutual repression is important for the specification of the embryonic body plan as ectopic expression of Mix.1 in the Xbra domain suppresses mesoderm differentiation. The same effect was obtained by overexpressing VP16Mix.1, a fusion protein comprising the strong activator domain of viral VP16 and the homeodomain of Mix.1, suggesting that Mix.1 acts as a transcriptional activator. Mix.1 also has a role in endoderm formation. It cooperates with the dorsal vegetal homeobox gene Siamois to activate the endodermal markers edd, Xlhbox8 and cerberus in animal caps. Conversely, vegetal overexpression of enRMix.1, an antimorphic Mix.1 mutant, leads to a loss of endoderm differentiation. Finally, by targeting enRMix.1 expression to the anterior endoderm, we could test the role of this tissue during embryogenesis and show that it is required for head formation.

Msx1 antagonizes the myogenic activity of Pax3 in migrating limb muscle precursors

Development ◽  
1999 ◽  
Vol 126 (22) ◽  
pp. 4965-4976 ◽  
Author(s):  
A.J. Bendall ◽  
J. Ding ◽  
G. Hu ◽  
M.M. Shen ◽  
C. Abate-Shen
Keyword(s):  
Protein Interactions ◽  
Myogenic Differentiation ◽  
Ectopic Expression ◽  
Homeobox Gene ◽  
Regulatory Elements ◽  
Limb Muscle ◽  
Chicken Embryos ◽  
Myogenic Activity ◽  
Myod Expression

The migration of myogenic precursors to the vertebrate limb exemplifies a common problem in development - namely, how migratory cells that are committed to a specific lineage postpone terminal differentiation until they reach their destination. Here we show that in chicken embryos, expression of the Msx1 homeobox gene overlaps with Pax3 in migrating limb muscle precursors, which are committed myoblasts that do not express myogenic differentiation genes such as MyoD. We find that ectopic expression of Msx1 in the forelimb and somites of chicken embryos inhibits MyoD expression as well as muscle differentiation. Conversely, ectopic expression of Pax3 activates MyoD expression, while co-ectopic expression of Msx1 and Pax3 neutralizes their effects on MyoD. Moreover, we find that Msx1 represses and Pax3 activates MyoD regulatory elements in cell culture, while in combination, Msx1 and Pax3 oppose each other's trancriptional actions on MyoD. Finally, we show that the Msx1 protein interacts with Pax3 in vitro, thereby inhibiting DNA binding by Pax3. Thus, we propose that Msx1 antagonizes the myogenic activity of Pax3 in migrating limb muscle precursors via direct protein-protein interaction. Our results implicate functional antagonism through competitive protein-protein interactions as a mechanism for regulating the differentiation state of migrating cells.

Identifying targets of the rough homeobox gene of Drosophila: evidence that rhomboid functions in eye development

Development ◽  
1992 ◽  
Vol 116 (2) ◽  
pp. 335-346 ◽  
Author(s):  
M. Freeman ◽  
B.E. Kimmel ◽  
G.M. Rubin
Keyword(s):  
Cell Fate ◽  
Target Genes ◽  
Eye Development ◽  
Expression Patterns ◽  
Ectopic Expression ◽  
Homeobox Gene ◽  
Homeodomain Protein ◽  
Dorsoventral Patterning ◽  
Altered Expression ◽  
Enhancer Trap Lines

In order to identify potential target genes of the rough homeodomain protein, which is known to specify some aspects of the R2/R5 photoreceptor subtype in the Drosophila eye, we have carried out a search for enhancer trap lines whose expression is rough-dependent. We crossed 101 enhancer traps that are expressed in the developing eye into a rough mutant background, and have identified seven lines that have altered expression patterns. One of these putative rough target genes is rhomboid, a gene known to be required for dorsoventral patterning and development of some of the nervous system in the embryo. We have examined the role of rhomboid in eye development and find that, while mutant clones have only a subtle phenotype, ectopic expression of the gene causes the non-neuronal mystery cells to be transformed into photoreceptors. We propose that rhomboid is a part of a partially redundant network of genes that specify photoreceptor cell fate.

A novel Xenopus mix-like gene milk involved in the control of the endomesodermal fates

Development ◽  
1998 ◽  
Vol 125 (14) ◽  
pp. 2577-2585 ◽  
Author(s):  
V. Ecochard ◽  
C. Cayrol ◽  
S. Rey ◽  
F. Foulquier ◽  
D. Caillol ◽  
...  
Keyword(s):  
Marginal Zone ◽  
Ectopic Expression ◽  
Homeobox Gene ◽  
Early Response ◽  
Response Gene ◽  
Mesodermal Cell ◽  
Early Response Gene ◽  
Mesoderm Formation ◽  
Definition Of ◽  
Early Gastrula

Here we describe a novel Xenopus homeobox gene, milk, related by sequence homology and expression pattern to the vegetally expressed Mix.1. As is the case with Mix.1, milk is an immediate early response gene to the mesoderm inducer activin. milk is expressed at the early gastrula stage in the vegetal cells, fated to form endoderm, and in the marginal zone fated to form mesoderm. During gastrulation, expression of milk becomes progressively reduced in the involuting mesodermal cells but is retained in the endoderm, suggesting that it may play a key role in the definition of the endo-mesodermal boundary in the embryo. Overexpression of milk in the marginal zone blocks mesodermal cell involution, represses the expression of several mesodermal genes such as Xbra, goosecoid, Xvent-1 or Xpo and increases the expression of the endodermal gene, endodermin. In the dorsal marginal zone, overexpression of milk leads to a severe late phenotype including the absence of axial structures. Ectopic expression of milk in the animal hemisphere or in ectodermal explants induces a strong expression of endodermin. Taken together, we propose that milk plays a role in the correct patterning of the embryo by repressing mesoderm formation and promoting endoderm identity.

Regulation of dorsal-ventral patterning: the ventralizing effects of the novel Xenopus homeobox gene Vox

Development ◽  
1996 ◽  
Vol 122 (6) ◽  
pp. 1711-1721 ◽  
Author(s):  
J.E. Schmidt ◽  
G. von Dassow ◽  
D. Kimelman
Keyword(s):  
Dynamic Process ◽  
Regulatory Network ◽  
Ectopic Expression ◽  
Homeobox Gene ◽  
Normal Function ◽  
Dorsal Side ◽  
Neural Plate ◽  
The Novel ◽  
Cell Fates ◽  
Early Developmental

The formation of the dorsal-ventral axis in Xenopus laevis is elicited by a signaling cascade on the dorsal side of the embryo initiated by cortical rotation. These early developmental events impart an initial axial polarity to the embryo. By the time gastrulation occurs, the embryo has established opposing dorsal and ventral regulatory regions. Through a dynamic process, the embryo acquires a definitive pattern that reflects the distribution of future cell fates. Here we present a novel homeobox gene, Vox, whose expression reflects this dynamic process. Vox is first expressed throughout the embryo and subsequently eliminated from the notochord and neural plate. Ectopic expression of Vox demonstrates that the normal function of this gene may be to suppress dorsal genes such as Xnot and chordin, and induce ventral and paraxial genes such as Bmp-4 and MyoD. Ectopic expression of BMP-4 ventralizes embryos and positively regulates the expression of Vox, suggesting that these genes are components of a reciprocal regulatory network.

The role of the NK-homeobox gene slouch (S59) in somatic muscle patterning

Development ◽  
1999 ◽  
Vol 126 (20) ◽  
pp. 4525-4535 ◽  
Author(s):  
S. Knirr ◽  
N. Azpiazu ◽  
M. Frasch
Keyword(s):  
Muscle Development ◽  
Ectopic Expression ◽  
Homeobox Gene ◽  
Drosophila Embryo ◽  
Loss Of Function ◽  
Cell Fates ◽  
Somatic Muscle ◽  
Gene Encoding ◽  
Body Wall Muscles ◽  
Founder Cells

In the Drosophila embryo, a distinct class of myoblasts, designated as muscle founders, prefigures the mature pattern of somatic body wall muscles. Each founder cell appears to be instrumental in generating a single larval muscle with a defined identity. The NK homeobox gene S59 was the first of a growing number of proposed ‘identity genes’ that have been found to be expressed in stereotyped patterns in specific subsets of muscle founders and their progenitor cells and are thought to control their developmental fates. In the present study, we describe the effects of gain- and loss-of-function experiments with S59. We find that a null mutation in the gene encoding S59, which we have named slouch (slou), disrupts the development of all muscles that are derived from S59-expressing founder cells. The observed phenotypes upon mutation and ectopic expression of slouch include transformations of founder cell fates, thus confirming that slouch (S59) functions as an identity gene in muscle development. These fate transformations occur between sibling founder cells as well as between neighboring founders that are not lineage-related. In the latter case, we show that slouch (S59) activity is required cell-autonomously to repress the expression of ladybird (lb) homeobox genes, thereby preventing specification along the lb pathway. Together, these findings provide new insights into the regulatory interactions that establish the somatic muscle pattern.

The Oncogenic Potential of the Homeobox Gene Cdx2 Is Depending on the MAPK Pathway and Can Be Antagonized by the MEK1/2 Inhibitor PD98059 in a Mouse Model of t(12;13)(p13;q12) Positive AML.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1975-1975
Author(s):  
Vijay P.S. Rawat ◽  
Vegi M. Naidu ◽  
Christina Schessl ◽  
Monica Cusan ◽  
R.Keith Humphries ◽  
...  
Keyword(s):  
Bone Marrow Cells ◽  
Fusion Gene ◽  
Mapk Pathway ◽  
Phosphorylation Site ◽  
Ectopic Expression ◽  
Homeobox Gene ◽  
Mapk Signaling ◽  
Transactivation Domain ◽  
Oncogenic Potential

Abstract In AML the translocation t(12;13)(p13;q12) results in the ectopic expression of the homeobox gene Cdx2 and the expression of the ETV6-CDX2 fusion. We have recently shown that myeloid leukemogenesis is induced by the ectopic expression of the proto-oncogene Cdx2 and not by the ETV6-CDX2 fusion gene in a murine model of t(12;13) AML. To characterize the contribution of different Cdx2 motifs to the transforming capacity of the gene we generated different mutants, inactivating the DNA binding homeodomain (N51S-Cdx2), or the PBX1-interacting motif (W167A-Cdx2), or deleting the N-terminal portion of Cdx2 (N-Cdx2). Expression of Cdx2 and the different mutants were induced in primary murine bone marrow cells by retroviral gene transfer, using an MSCV based retroviral construct with an IRES-YFP cassette. Expression of Cdx2 and the W167A-Cdx2 mutant significantly increased primary colony formation (3-fold) (n=3;p<0.001) with a higher number of CFU-G/GM colonies (p<0.015). Furthermore, both constructs enhanced the replating capacity of clonogenic progenitors with an 80-100fold increase in secondary colonies (p<0.005). In addition, both constructs induced the outgrowth of blast colonies (2700fold; p<0.02). In contrast, cells transduced with N51S-Cdx2 and N-Cdx2 lost their clonogenic potential after replating. In vivo all mice transplanted with cells expressing Cdx2 or the W167A-Cdx2 mutant developed transplantable AML. However, in Cdx2 leukemic mice > 90% of the cells co-expressed Gr-1+ and Mac1+, whereas in W167A mice 40% of the leukemic population were Gr-1+ only. The N51S mutant induced a distinct leukemia phenotype with 90 % Gr-1+/c-Kit+. We extended structure-function analyses, inactivating the phosphorylation site (S60) in the Cdx2 transactivation domain, previously shown to be regulated by the MAPK family. We confirmed that oncogenic Cdx2 is phophorylated at the N-terminal in primary BM cells by Western blotting using a P-Cdx2-S60 specific antibody. S60 position mutation slightly reduced the hematopoietic activity of wild-type Cdx2. Incubation with the MEK1 inhibitor PD98059 inhibited phosphorylation, decreased the frequency of CFU-S 8fold (n=7; p<0.001) and blocked growth of leukemic Cdx2 transfected blasts in vitro. In contrast, the p38 inhibitor SB2059 did not prevent phosphorylation and was unable to antagonize Cdx2 induced transformation. These data demonstrate that the transforming activity of Cdx2 and the phenotype of Cdx2 induced leukemias is depending on the functional integrity of distinct Cdx2 domains. Furthermore, our data link the oncogenic potential of Cdx2 directly to the MAPK signaling, opening the possibility to counteract Cdx2 associated leukemogenesis by kinase inhibitors.

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