Mesendoderm and left-right brain, heart and gut development are differentially regulated by pitx2 isoforms

Development ◽  
2000 ◽  
Vol 127 (5) ◽  
pp. 1081-1093 ◽  
Author(s):  
J.J. Essner ◽  
W.W. Branford ◽  
J. Zhang ◽  
H.J. Yost
Keyword(s):  
Expression Patterns ◽  
Ectopic Expression ◽  
Dorsal Side ◽  
Organ Development ◽  
Gut Development ◽  
Prechordal Plate ◽  
Pitx2 Gene ◽  
Isoform Expression ◽  
Left Right Asymmetry ◽  
Molecular Phenotypes

The pitx2 gene is a member of the bicoid-homeodomain class of transcription factors that has been implicated in the control of left-right asymmetry during organogenesis. Here we demonstrate that in zebrafish there are two pitx2 isoforms, pitx2a and pitx2c, which show distinct expression patterns and have non-overlapping functions during mesendoderm and asymmetric organ development. pitx2c is expressed symmetrically in presumptive mesendoderm during late blastula stages and in the prechordal plate during late gastrulation. pitx2a expression is first detected at bud stage in the anterior prechordal plate. The regulation of early mesendoderm pitx2c expression is dependent on one-eyed pinhead (EGF-CFC-related gene) and spadetail (tbx-transcription factor) and can be induced by ectopic goosecoid expression. Maintenance of pitx2c midline expression is dependent on cyclops (nodal) and schmalspur, but not no tail (brachyury). Ectopic expression of pitx2 isoforms results in distinct morphological and molecular phenotypes, indicating that pitx2a and pitx2c have divergent regulatory functions. Both isoforms downregulate goosecoid on the dorsal side, but in contrast to earlier reports that nodal and lefty are upstream of pitx2, ectopic pitx2c in other regions induces cyclops, lefty2 and goosecoid expression. Asymmetric isoform expression occurs in non-overlapping domains, with pitx2c in left dorsal diencephalon and developing gut and pitx2a in left heart primordium. Targeted asymmetric expression in Xenopus shows that both isoforms can alter left-right development, but pitx2a has a slightly stronger effect on heart laterality. Our results indicate that distinct genetic pathways regulate pitx2a and pitx2c isoform expression, and each isoform regulates different downstream pathways during mesendoderm and asymmetric organ development.

Regulation of midline development by antagonism of lefty and nodal signaling

Development ◽  
1999 ◽  
Vol 126 (14) ◽  
pp. 3253-3262 ◽  
Author(s):  
B.W. Bisgrove ◽  
J.J. Essner ◽  
H.J. Yost
Keyword(s):  
Expression Patterns ◽  
Ectopic Expression ◽  
Bilateral Symmetry ◽  
Expression Domain ◽  
Lateral Plate ◽  
Altered Expression ◽  
Left Right Asymmetry ◽  
Midline Development ◽  
Additional Role ◽  
Pitx2 Expression

The embryonic midline is crucial for the development of embryonic pattern including bilateral symmetry and left-right asymmetry. In zebrafish, lefty1 (lft1) and lefty2 (lft2) have distinct midline expression domains along the anteroposterior axis that overlap with the expression patterns of the nodal-related genes cyclops and squint. Altered expression patterns of lft1 and lft2 in zebrafish mutants that affect midline development suggests different upstream pathways regulate each expression domain. Ectopic expression analysis demonstrates that a balance of lefty and cyclops signaling is required for normal mesendoderm patterning and goosecoid, no tail and pitx2 expression. In late somite-stage embryos, lft1 and lft2 are expressed asymmetrically in the left diencephalon and left lateral plate respectively, suggesting an additional role in laterality development. A model is proposed by which the vertebrate midline, and thus bilateral symmetry, is established and maintained by antagonistic interactions among co-expressed members of the lefty and nodal subfamilies of TGF-beta signaling molecules.

scholarly journals Analysis of maxillopedia Expression Pattern and Larval Cuticular Phenotype in Wild-Type and Mutant Tribolium

Genetics ◽  
2000 ◽  
Vol 155 (2) ◽  
pp. 721-731 ◽  
Author(s):  
Teresa D Shippy ◽  
Jianhua Guo ◽  
Susan J Brown ◽  
Richard W Beeman ◽  
Robin E Denell
Keyword(s):  
Rna Interference ◽  
Expression Pattern ◽  
Tribolium Castaneum ◽  
Expression Patterns ◽  
Ectopic Expression ◽  
Homeotic Gene ◽  
Wild Type ◽  
Double Stranded Rna ◽  
Similar Expression ◽  
Mutant Phenotypes

Abstract The Tribolium castaneum homeotic gene maxillopedia (mxp) is the ortholog of Drosophila proboscipedia (pb). Here we describe and classify available mxp alleles. Larvae lacking all mxp function die soon after hatching, exhibiting strong transformations of maxillary and labial palps to legs. Hypomorphic mxp alleles produce less severe transformations to leg. RNA interference with maxillopedia double-stranded RNA results in phenocopies of mxp mutant phenotypes ranging from partial to complete transformations. A number of gain-of-function (GOF) mxp alleles have been isolated based on transformations of adult antennae and/or legs toward palps. Finally, we have characterized the mxp expression pattern in wild-type and mutant embryos. In normal embryos, mxp is expressed in the maxillary and labial segments, whereas ectopic expression is observed in some GOF variants. Although mxp and Pb display very similar expression patterns, pb null embryos develop normally. The mxp mutant larval phenotype in Tribolium is consistent with the hypothesis that an ancestral pb-like gene had an embryonic function that was lost in the lineage leading to Drosophila.

pha-4 is Ce-fkh-1, a fork head/HNF-3alpha, beta, gamma homolog that functions in organogenesis of the C. elegans pharynx

Development ◽  
1998 ◽  
Vol 125 (12) ◽  
pp. 2171-2180 ◽  
Author(s):  
J.M. Kalb ◽  
K.K. Lau ◽  
B. Goszczynski ◽  
T. Fukushige ◽  
D. Moons ◽  
...  
Keyword(s):  
Early Stage ◽  
Sequence Similarity ◽  
Expression Patterns ◽  
Ectopic Expression ◽  
Specific Gene ◽  
Gata Factor ◽  
Enhancer Element ◽  
C Elegans ◽  
Fork Head ◽  
Organ Identity

The C. elegans Ce-fkh-1 gene has been cloned on the basis of its sequence similarity to the winged-helix DNA binding domain of the Drosophila fork head and mammalian HNF-3alpha, beta, gamma genes, and mutations in the zygotically active pha-4 gene have been shown to block formation of the pharynx (and rectum) at an early stage in embryogenesis. In the present paper, we show that Ce-fkh-1 and pha-4 are the same gene. We show that PHA-4 protein is present in nuclei of essentially all pharyngeal cells, of all five cell types. PHA-4 protein first appears close to the point at which a cell lineage will produce only pharyngeal cells, independently of cell type. We show that PHA-4 binds directly to a ‘pan-pharyngeal enhancer element’ previously identified in the promoter of the pharyngeal myosin myo-2 gene; in transgenic embryos, ectopic PHA-4 activates ectopic myo-2 expression. We also show that ectopic PHA-4 can activate ectopic expression of the ceh-22 gene, a pharyngeal-specific NK-2-type homeodomain protein previously shown to bind a muscle-specific enhancer near the PHA-4 binding site in the myo-2 promoter. We propose that it is the combination of pha-4 and regulatory molecules such as ceh-22 that produces the specific gene expression patterns during pharynx development. Overall, pha-4 can be described as an ‘organ identity factor’, completely necessary for organ formation, present in all cells of the organ from the earliest stages, capable of integrating upstream developmental pathways (in this case, the two distinct pathways that produce the anterior and posterior pharynx) and participating directly in the transcriptional regulation of organ specific genes. Finally, we note that the distribution of PHA-4 protein in C. elegans embryos is remarkably similar to the distribution of the fork head protein in Drosophila embryos: high levels in the foregut/pharynx and hindgut/rectum; low levels in the gut proper. Moreover, we show that pha-4 expression in the C. elegans gut is regulated by elt-2, a C. elegans gut-specific GATA-factor and possible homolog of the Drosophila gene serpent, which influences fork head expression in the fly gut. Overall, our results provide evidence for a highly conserved pathway regulating formation of the digestive tract in all (triploblastic) metazoa.

scholarly journals FOXP2 exhibits projection neuron class specific expression, but is not required for multiple aspects of cortical histogenesis

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Ryan J Kast ◽  
Alexandra L Lanjewar ◽  
Colton D Smith ◽  
Pat Levitt
Keyword(s):  
Expression Patterns ◽  
Projection Neuron ◽  
Specific Expression ◽  
Neuron Populations ◽  
Mouse Cortex ◽  
Molecular Studies ◽  
Multiple Species ◽  
Molecular Phenotypes ◽  
And Function

The expression patterns of the transcription factor FOXP2 in the developing mammalian forebrain have been described, and some studies have tested the role of this protein in the development and function of specific forebrain circuits by diverse methods and in multiple species. Clinically, mutations in FOXP2 are associated with severe developmental speech disturbances, and molecular studies indicate that impairment of Foxp2 may lead to dysregulation of genes involved in forebrain histogenesis. Here, anatomical and molecular phenotypes of the cortical neuron populations that express FOXP2 were characterized in mice. Additionally, Foxp2 was removed from the developing mouse cortex at different prenatal ages using two Cre-recombinase driver lines. Detailed molecular and circuit analyses were undertaken to identify potential disruptions of development. Surprisingly, the results demonstrate that Foxp2 function is not required for many functions that it has been proposed to regulate, and therefore plays a more limited role in cortical development than previously thought.

scholarly journals TGF-β and the Smad Signaling Pathway Support Transcriptomic Reprogramming during Epithelial-Mesenchymal Cell Transition

2005 ◽  
Vol 16 (4) ◽  
pp. 1987-2002 ◽  
Author(s):  
Ulrich Valcourt ◽  
Marcin Kowanetz ◽  
Hideki Niimi ◽  
Carl-Henrik Heldin ◽  
Aristidis Moustakas
Keyword(s):  
Target Genes ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Smooth Muscle Actin ◽  
Expression Patterns ◽  
Ectopic Expression ◽  
Dominant Negative ◽  
Type I ◽  
Mesenchymal Transition ◽  
Smad Signaling

Epithelial-mesenchymal transition (EMT) contributes to normal tissue patterning and carcinoma invasiveness. We show that transforming growth factor (TGF)-β/activin members, but not bone morphogenetic protein (BMP) members, can induce EMT in normal human and mouse epithelial cells. EMT correlates with the ability of these ligands to induce growth arrest. Ectopic expression of all type I receptors of the TGF-β superfamily establishes that TGF-β but not BMP pathways can elicit EMT. Ectopic Smad2 or Smad3 together with Smad4 enhanced, whereas dominant-negative forms of Smad2, Smad3, or Smad4, and wild-type inhibitory Smad7, blocked TGF-β–induced EMT. Transcriptomic analysis of EMT kinetics identified novel TGF-β target genes with ligand-specific responses. Using a TGF-β type I receptor that cannot activate Smads nor induce EMT, we found that Smad signaling is critical for regulation of all tested gene targets during EMT. One such gene, Id2, whose expression is repressed by TGF-β1 but induced by BMP-7 is critical for regulation of at least one important myoepithelial marker, α-smooth muscle actin, during EMT. Thus, based on ligand-specific responsiveness and evolutionary conservation of the gene expression patterns, we begin deciphering a genetic network downstream of TGF-β and predict functional links to the control of cell proliferation and EMT.

Cardiac looping and the vertebrate left-right axis: antagonism of left-sided Vg1 activity by a right-sided ALK2-dependent BMP pathway

Development ◽  
1999 ◽  
Vol 126 (23) ◽  
pp. 5195-5205 ◽  
Author(s):  
A.F. Ramsdell ◽  
H.J. Yost
Keyword(s):  
Signaling Pathway ◽  
Expression Patterns ◽  
Ectopic Expression ◽  
Xenopus Embryo ◽  
Receptor Expression ◽  
Heart Tube ◽  
Cardiac Morphogenesis ◽  
Heart Looping ◽  
Bmp Pathway ◽  
The Right

The rightward looping of the primary heart tube is dependent upon upstream patterning events that establish the vertebrate left-right axis. In Xenopus, a left-sided Vg1 signaling pathway has been implicated in instructing cells to adopt a ‘left-sided identity’; however, it is not known whether ‘right-sided identity’ is acquired by a default pathway or by antagonism of Vg1 signaling. Here, we propose that an antagonistic, BMP/ALK2/Smad-mediated signaling pathway is active on the right side of the Xenopus embryo. Truncated ALK2 receptor expression on the right side of the blastula elicits heart reversals and altered nodal expression. Consistent with these findings, constitutively active ALK2 (CA-ALK2) receptor expression on the left side of the blastula also elicits heart reversals and altered nodal expression. Coexpression of CA-ALK2 with mature Vg1 ligand results in predominantly left-sided nodal expression patterns and normal heart looping, demonstrating that the ALK2 pathway can ‘rescue’ left-right reversals that otherwise occur following right-sided misexpression of mature Vg1 ligand alone. Results with chimeric precursor proteins indicate that the mature domain of BMP ligands can mimic the ability of the ALK2 signaling pathway to antagonize the Vg1 pathway. Consistent with the observed antagonism between BMP and Vg1 ligands, left-sided ectopic expression of Xolloid results in heart reversals. Moreover, ectopic expression of Smad1 or Smad7 identified two downstream modulators of the BMP/ALK2 signaling pathway that also can regulate cardiac orientation. Collectively, these results define a BMP/ALK2-mediated pathway on the right side of the Xenopus embryo and, moreover, suggest that left-right patterning preceding cardiac morphogenesis involves the activation of two distinct and antagonistic, left- and right-sided TGF(beta)-related signaling pathways.

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.

Sonic hedgehog is not required for polarising activity in the Doublefoot mutant mouse limb bud

Development ◽  
1998 ◽  
Vol 125 (3) ◽  
pp. 351-357 ◽  
Author(s):  
C. Hayes ◽  
J.M. Brown ◽  
M.F. Lyon ◽  
G.M. Morriss-Kay
Keyword(s):  
Gene Expression ◽  
Limb Development ◽  
Target Genes ◽  
Anterior Part ◽  
Expression Patterns ◽  
Ectopic Expression ◽  
Mutant Gene ◽  
Limb Bud ◽  
Active Constituent ◽  
Limb Buds

The mouse mutant Doublefoot (Dbf) shows preaxial polydactyly of all four limbs. We have analysed limb development in this mutant with respect to morphogenesis, gene expression patterns and ectopic polarising activity. The results reveal a gain-of-function mutation at a locus that mediates pattern formation in the developing limb. Shh expression is identical with that of wild-type embryos, i.e. there is no ectopic expression. However, mesenchyme from the anterior aspects of Dbf/+ mutant limb buds, when transplanted to the anterior side of chick wing buds, induces duplication of the distal skeletal elements. Mid-distal mesenchymal transplants from early, but not later, Dbf/+ limb buds are also able to induce duplication. This demonstration of polarising activity in the absence of Shh expression identifies the gene at the Dbf locus as a new genetic component of the Shh signalling pathway, which (at least in its mutated form) is able to activate signal transduction independently of Shh. The mutant gene product is sufficient to fulfil the signalling properties of Shh including upregulation of the direct Shh target genes Ptc and Gli, and induction of the downstream target genes Bmp2, Fgf4 and Hoxd13. The expression domains of all these genes extend from their normal posterior domains into the anterior part of the limb bud without being focused on a discrete ectopic site. These observations dissociate polarising activity from Shh gene expression in the Dbf/+ limb bud. We suggest that the product of the normal Dbf gene is a key active constituent of the polarising region, possibly acting in the extracellular compartment.

BMPs are necessary for stomach gland formation in the chicken embryo: a study using virally induced BMP-2 and Noggin expression

Development ◽  
2000 ◽  
Vol 127 (5) ◽  
pp. 981-988 ◽  
Author(s):  
T. Narita ◽  
K. Saitoh ◽  
T. Kameda ◽  
A. Kuroiwa ◽  
M. Mizutani ◽  
...  
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Chicken Embryo ◽  
Normal Development ◽  
Expression Patterns ◽  
Ectopic Expression ◽  
Complete Inhibition ◽  
Glandular Stomach ◽  
Digestive Organs ◽  
Chicken Proventriculus ◽  
Inductive Signals

Epithelial-mesenchymal interactions are necessary for the normal development of various digestive organs. In chicken proventriculus (glandular stomach), morphogenesis and differentiation of the epithelium depend upon the inductive signals coming from underlying mesenchyme. However, the nature of such signals is still unclear despite extensive analyses carried out using experimental tissue recombinations. In this study we have examined the possible involvement of bone morphogenetic proteins (BMPs) in the formation of stomach glands in the chicken embryo. Analysis of the expression patterns of BMP-2, −4 and −7 showed that these BMPs were present in the proventricular mesenchyme prior to the initiation of the proventricular gland formation. BMP-2 expression, in particular, was restricted to the proventriculus among anterior digestive organs. Virus-mediated BMP-2 overexpression resulted in an increase in the number of glands formed. Moreover, ectopic expression of Noggin, which antagonizes the effect of BMPs, in the proventricular mesenchyme or epithelium, led to the complete inhibition of gland formation, indicating that BMP signals are necessary for the proventricular gland formation. These findings suggest that BMPs are of prime importance as mesenchymal signals for inducing proventricular glands.

Control of GL2 expression in Arabidopsis leaves and trichomes

Development ◽  
1998 ◽  
Vol 125 (7) ◽  
pp. 1161-1171 ◽  
Author(s):  
D.B. Szymanski ◽  
R.A. Jilk ◽  
S.M. Pollock ◽  
M.D. Marks
Keyword(s):  
Cell Expansion ◽  
Expression Patterns ◽  
Ectopic Expression ◽  
Spatial And Temporal Variation ◽  
R Gene ◽  
Gus Reporter ◽  
Transparent Testa ◽  
Initial Selection ◽  
Epistatic Analysis ◽  
Selection Of

More than twenty genes are required for the correct initiation, spacing, and morphogenesis of trichomes in Arabidopsis. The initial selection of trichome precursors requires the activity of both the GLABROUS1 (GL1) and TRANSPARENT TESTA GLABROUS (TTG) genes. The GLABRA2 (GL2) gene is required for subsequent phases of trichome morphogenesis such as cell expansion, branching, and maturation of the trichome cell wall. Previous studies have shown that GL2 is a member of the homeodomain class of transcription factors. Here we report a detailed analysis of GL2 expression in the shoot using anti-GL2 antibodies and the GUS reporter gene fused to the GL2 promoter. The GL2 expression profile in the shoot is complex, and involves spatial and temporal variation in developing leaves and trichomes. Two separate promoter domains that are expressed in trichomes were identified. GL2, like GL1, is expressed in developing trichomes and in cells surrounding trichomes during early stages of trichome development. Unlike GL1, GL2 expression persists in mature trichomes. It was found that while GL1 and TTG were not required for the initiation of GL2 expression in the non-trichome cells, the presence of a functional GL1 or TTG gene was able to increase GL2 expression in these cells compared to ttg gl1 plants. The hypothesis that GL1 regulates aspects of GL2 expression is consistent with epistatic analysis of gl1 and gl2 and the expression patterns of GL1 and GL2. In support of this hypothesis, it was found that ectopic expression of GL1 in the presence of ectopic expression of the maize R gene, which can bypass the requirement for TTG, can ectopically activate GL2 transcription.

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