SEARCH · PubMed Health

Results for “spatial domain identification”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources

PubMed2001

Distinct roles of maf genes during Xenopus lens development.

Lens development provides a good model system for studying cellular and molecular mechanisms underlying embryonic induction and morphogenesis. Members of the large Maf family of transcription factors, L-Maf and c-Maf, have been shown to play key roles in chick and mouse lens development. Here we report identification of two Xenopus maf genes, XmafB and XL-maf, which exhibit unique temporal and spatial expression patterns during lens formation. XmafB can first be detected in the presumptive lens-forming ectoderm, when the primary eye vesicle makes contact with the head ectoderm. XL-maf expression appears a little later, just before thickening of the lens placode, and both XmafB and XL-maf can be detected in the lens placode. During lens vesicle formation, the expression domains of XmafB and XL-maf segregated from each other, resulting in restricted expression in lens epithelial and fiber cells, respectively. When the optic cup anlagen was removed, only XmafB expression is detected. Both Mafs can induce the lens fiber cell-specific markers, betaA4- and gamma-crystallins. In animal cap assays, XmafB can induce Pax6, Xlens1 and Sox3 expression, but XL-maf fails to induce Pax6 and Xlens1 expression. These results suggest that these maf genes are involved in the regulation of cell-type specific gene expression and play roles in inductive events during Xenopus lens development.

Animals↗

PubMed2005

ZNF649, a novel Kruppel type zinc-finger protein, functions as a transcriptional suppressor.

Cardiac differentiation involves a cascade of coordinated gene expression that regulates cell proliferation and matrix protein formation in a defined temporo-spatial manner. Many of the KRAB-ZFPs are involved in cardiac development or cardiovascular diseases. Here we report the identification and characterization of a novel human zinc-finger gene named ZNF649. The cDNA of ZNF649 is 3176 bp, encoding a protein of 505 amino acids in the nuclei. Northern blot analysis indicates that ZNF649 is expressed in most of the examined human adult and embryonic tissues. ZNF649 is a transcription suppressor when fused to GAL-4 DNA-binding domain and cotransfected with VP-16. Overexpression of ZNF649 in COS-7 cells inhibits the transcriptional activities of SRE and AP-1. Deletion analysis with a series of truncated fusion proteins indicates that the KRAB motif is a basal repression domain when the truncated fusion proteins were assayed for the transcriptional activities of SRE and AP-1. These results suggest that ZNF649 protein may act as a transcriptional repressor in mitogen-activated protein kinase signaling pathway to mediate cellular functions.

Amino Acid Sequence↗

PubMed2000

Temporal and spatial determination of EEG-seizure onset in the frequency domain.

OBJECTIVE: A quantitative analysis of scalp electric fields in patients suffering from pharmacoresistant temporal lobe epilepsy was performed in order to study the development of rhythmic ictal activities over time. METHODS: A method that calculates phase-corrected voltage maps in the frequency domain (FFT-approximation) was applied to ictal multichannel recordings in 10 epileptic patients. The onset of the ictally dominant frequency was determined and its temporal evolution over a time period of 46 s around the ictal EEG onset was studied. The analysis was completed by a linear inverse solution that estimated the sources of the dominant frequency. RESULTS: This method permitted the identification of an ictally dominant frequency which started on the average prior to the onset of initial EEG signs as determined by visual inspection. The frequency incremented during the evolution of the seizure in all patients. The linear inverse solution algorithm localized the source of this frequency to the brain region which was clinically determined as the site of seizure onset and whose resection rendered all patients seizure-free. CONCLUSIONS: Our data suggest that the constant increase of the ictally dominant frequency is related to the amount of temporal lobe tissue generating the ictal discharges. Frequential analysis of ictal electric fields can be reliably used to detect focal pathological activity early during seizure onset arising in deep structures such as the mesial temporal lobe.

Adult↗

PubMed2003

Regulation of alternative splicing of Gtf2ird1 and its impact on slow muscle promoter activity.

A human MusTRD (muscle TFII-I repeat domain (RD)-containing protein) isoform was originally identified in a yeast one-hybrid screen as a protein that binds the slow fibre-specific enhancer of the muscle gene troponin I slow [O'Mahoney, Guven, Lin, Joya, Robinson, Wade and Hardeman (1998) Mol. Cell. Biol. 18, 6641-6652]. MusTRD shares homology with the general transcription factor TFII-I by the presence of diagnostic I-RDs [Roy (2001) Gene 274, 1-13]. The human gene encoding MusTRD, GTF2IRD1 ( WBSCR11 / GTF3 ), was subsequently located on chromosome 7q11.23, a region deleted in the neurodegenerative disease, Williams-Beuren Syndrome [Osborne, Campbell, Daradich, Scherer, Tsui, Franke, Peoples, Francke, Voit, Kramer et al. (1999) Genomics 57, 279-284; Franke, Peoples and Francke (1999) Cytogenet. Cell. Genet. 86, 296-304; Tassabehji, Carette, Wilmot, Donnai, Read and Metcalfe (1999) Eur. J. Hum. Genet. 7, 737-747]. The haploinsufficiency of MusTRD has been implicated in the myopathic aspect of this disease, which manifests itself in symptoms such as lowered resistance to fatigue, kyphoscoliosis, an abnormal gait and joint contractures [Tassabehji, Carette, Wilmot, Donnai, Read and Metcalfe (1999) Eur. J. Hum. Genet. 7, 737-747]. Here, we report the identification of 11 isoforms of MusTRD in mouse skeletal muscles. These isoforms were isolated from a mouse skeletal muscle cDNA library and reverse transcription-PCR on RNA from various adult and embryonic muscles. The variability in these isoforms arises from alternative splicing of a combination of four cassettes and two mutually exclusive exons, all in the 3' region of the primary transcript of Gtf2ird1, the homologous mouse gene. The expression of some of these isoforms is differentially regulated spatially, suggesting individual regulation of the expression of these isoforms. Co-transfection studies in C2C12 muscle cell cultures reveal that isoforms differentially regulate muscle fibre-type-specific promoters. This indicates that the presence of different domains of MusTRD influences the activity exerted by this molecule on multiple promoters active in skeletal muscle.

Alternative Splicing↗

PubMed2001

Identification of a monofunctional aspartate kinase gene of Arabidopsis thaliana with spatially and temporally regulated expression.

We screened a gene trap library of Arabidopsis thaliana and isolated a line in which a gene encoding a homologue of monofunctional aspartate kinase was trapped by the reporter gene. Aspartate kinase (AK) is a key enzyme in the biosynthsis of aspartate family amino acids such as lysine, threonine, isoleucine, and methionine. In plants, two types of AK are known: one is AK which is sensitive to feedback inhibition by threonine and carries both AK and homoserine dehydrogenase (HSD) activities. The other one is monofunctional, sensitive to lysine and synergistically S-adenosylmethionine, and has only AK activity. We concluded that the trapped gene encoded a monofunctional aspartate kinase and designated as AK-lys3, because it lacked the HSD domain and had an amino acid sequence highly similar to those of the monofunctional aspartate kinases ofA. thaliana. AK-lys3 was highly expressed in xylem of leaves and hypocotyls and stele of roots. Significant expression of this gene was also observed in trichomes after bolting. Slight expression of AK-lys3 was detected in vascular bundles and mesophyll cells of cauline leaves, inflorescence stems, sepals, petals, and stigmas. These results indicated that this aspartate kinase gene was not expressed uniformly but in a spatially specific manner.

Amino Acid Sequence↗

PubMed2025

Functional characterization of DPP4 and FcRn as receptor and coreceptor for classical human astroviruses in Caco-2 cells.

Classical human astroviruses (HAstV) are a global cause of viral gastroenteritis, particularly in children and immunocompromised individuals. Despite their clinical significance, the biology of HAstV remains poorly understood. In particular, the identification of cellular receptors and coreceptors has been elusive. Recent studies have identified the human neonatal Fc receptor (FcRn) as a functional receptor and dipeptidyl peptidase IV (DPP4) as an entry factor for HAstV. However, the precise roles of FcRn and DPP4 during HAstV infection are unknown. To learn about their function, we used FcRn-knockout (KO), DPP4-KO, and FcRn/DPP4 double-KO Caco-2 cells generated via CRISPR/Cas9. Our results showed that DPP4 serves as the receptor for classical HAstV. In contrast, infectious virus assays and confocal fluorescence microscopy revealed that FcRn acts as a coreceptor, facilitating viral internalization and the release of the RNA genome. The half-time for HAstV-1 genome uncoating was delayed threefold in FcRn-KO Caco-2 cells compared to WT cells. Additionally, the characterization of HAstV-8 variants with reduced FcRn binding capacity allowed the identification of two amino acids in the viral capsid spike protein, D471 and N512, critical for the spike-FcRn interaction. These amino acid residues are part of the epitope footprint of neutralizing monoclonal antibodies (Nt-MAbs) to HAstV previously mapped by X-ray crystallography. Further experiments using virus infectivity and attachment assays, along with Nt-MAbs targeting HAstV-1, suggest that the binding sites for FcRn and DPP4 are spatially proximal on the viral spike, defining a functional domain for cell infection. Notably, the infectivity of the divergent HAstV-VA1 was independent of these two proteins, highlighting the receptor variability across HAstV clades. These findings provide new insights into the mechanism of HAstV infection, offering relevant implications for the development of antiviral therapies and vaccines targeting this significant human pathogen.

Humans↗

PubMed2005

Identification and analysis of Hic-5/ARA55 isoforms: Implications for integrin signaling and steroid hormone action.

Hic-5/ARA55 is a LIM-only member of the paxillin superfamily. Conflicting reports have suggested that Hic-5/ARA55 can both repress and enhance a number of biological processes, including myogenesis and tumorigenesis. With two Hic-5 isoforms documented, we hypothesized that multiple Hic-5 isoforms may exist that have both overlapping and isoform-specific functions. To test this hypothesis, we performed an extensive analysis of Hic-5 transcripts in both cell lines and mouse tissues and found 12 distinct isoforms that fall into two sub-families. These isoforms are derived from both alternative splicing and alternative transcriptional start sites (TSS). Hic-5 expression is regulated in a temporally and spatially controlled manner in vivo. The identification of numerous Hic-5 isoforms suggests that Hic-5 subsumes a number of distinct roles in cells and may explain the range of biological responses attributed to Hic-5.

Alternative Splicing↗

PubMed2002

A provisional regulatory gene network for specification of endomesoderm in the sea urchin embryo.

We present the current form of a provisional DNA sequence-based regulatory gene network that explains in outline how endomesodermal specification in the sea urchin embryo is controlled. The model of the network is in a continuous process of revision and growth as new genes are added and new experimental results become available; see http://www.its.caltech.edu/~mirsky/endomeso.htm (End-mes Gene Network Update) for the latest version. The network contains over 40 genes at present, many newly uncovered in the course of this work, and most encoding DNA-binding transcriptional regulatory factors. The architecture of the network was approached initially by construction of a logic model that integrated the extensive experimental evidence now available on endomesoderm specification. The internal linkages between genes in the network have been determined functionally, by measurement of the effects of regulatory perturbations on the expression of all relevant genes in the network. Five kinds of perturbation have been applied: (1) use of morpholino antisense oligonucleotides targeted to many of the key regulatory genes in the network; (2) transformation of other regulatory factors into dominant repressors by construction of Engrailed repressor domain fusions; (3) ectopic expression of given regulatory factors, from genetic expression constructs and from injected mRNAs; (4) blockade of the beta-catenin/Tcf pathway by introduction of mRNA encoding the intracellular domain of cadherin; and (5) blockade of the Notch signaling pathway by introduction of mRNA encoding the extracellular domain of the Notch receptor. The network model predicts the cis-regulatory inputs that link each gene into the network. Therefore, its architecture is testable by cis-regulatory analysis. Strongylocentrotus purpuratus and Lytechinus variegatus genomic BAC recombinants that include a large number of the genes in the network have been sequenced and annotated. Tests of the cis-regulatory predictions of the model are greatly facilitated by interspecific computational sequence comparison, which affords a rapid identification of likely cis-regulatory elements in advance of experimental analysis. The network specifies genomically encoded regulatory processes between early cleavage and gastrula stages. These control the specification of the micromere lineage and of the initial veg(2) endomesodermal domain; the blastula-stage separation of the central veg(2) mesodermal domain (i.e., the secondary mesenchyme progenitor field) from the peripheral veg(2) endodermal domain; the stabilization of specification state within these domains; and activation of some downstream differentiation genes. Each of the temporal-spatial phases of specification is represented in a subelement of the network model, that treats regulatory events within the relevant embryonic nuclei at particular stages.

Animals↗

PubMed1999

Dyscalculia in the early stages of Alzheimer's disease.

OBJECTIVE: To study mathematical deficits in the early stages of Alzheimer's disease (AD). METHODS: Sixty-eight patients with mild AD and 242 normal controls (NC) received a standardized battery (EC 301-R) assessing number processing and calculation abilities. AD patients also received testing for language, memory, visuo-spatial and executive-attentional domains. RESULTS: Sixty-four AD patients (94.1%) showed impaired performances on the EC 301-R. Mathematical deficits were evident both on calculation and number processing skills. Performance on the single tasks was related to attentional-executive resources and to impaired number representations. Heterogeneous patterns of preserved/impaired mathematical abilities were also observed in single cases. CONCLUSION: Dyscalculia is an early sign of AD. It should be included among the reliable clinical hallmarks for the diagnosis of AD. Identification of dyscalculic symptoms in these patients requires composite assessment procedure.

Aged↗

PubMedDate not supplied

Identification and spatial distribution of retinoids in the developing chick limb bud.

All-trans-retinoic acid (RA) induces striking digit pattern duplications when locally applied to the developing chick limb bud. Instead of the normal digit pattern (234) a mirror-symmetrical 432234 pattern can be specified. Hence, RA closely mimics posterior limb bud tissue (the zone of polarizing activity, ZPA) that causes very similar duplications when grafted to an anterior site of a host limb bud. This resemblance raises an intriguing possibility: that RA is related to the as yet unidentified inducer substance thought to be released by the ZPA. Here we report that chick limb buds contain endogenous RA and we show that RA, but not its biosynthetic precursor retinol, forms a concentration gradient across the limb anlage with a high-point in the posterior domain of the limb bud, the part that also contains the ZPA.

Animals↗

PubMed2004

Simultaneous storage of patient information with medical images in the frequency domain.

Digital watermarking is a technique of hiding specific identification data for copyright authentication. Most of the medical images are compressed by joint photographic experts group (JPEG) standard for storage. The watermarking is adapted here for interleaving patient information with medical images during JPEG compression, to reduce storage and transmission overheads. The text data is encrypted before interleaving with images in the frequency domain to ensure greater security. The graphical signals are also interleaved with the image. The result of this work is tabulated for a specific example and also compared with the spatial domain interleaving.

Algorithms↗

PubMed1998

Molecular characterization of the zebrafish PEA3 ETS-domain transcription factor.

The PEA3 subfamily of ETS-domain proteins play important roles in regulating transcriptional activation and have been implicated in several tumorigenic processes. Here we describe the identification of a further member of this family from zebrafish which most likely represents a homologue of PEA3. A high degree of sequence conservation is observed in the ETS DNA-binding domain and acidic transcriptional activation domain. The DNA binding specificity of zebrafish PEA3 is virtually identical to that exhibited by mammalian family members and is autoregulated by cisacting inhibitory domains. Transcriptional activation by zebrafish PEA3 is potentiated by the ERK MAP kinase and protein kinase A pathways. During embryogenesis, PEA3 is expressed in complex spatial and temporal patterns in both mesodermal somites and ectodermal tissues including the brain, dorsal spinal chord and neural crest. Our characterisation of zebrafish PEA3 furthers our understanding of its molecular function and its expression profile suggests a novel role in cell patterning in the early vertebrate embryo.

Amino Acid Sequence↗

PubMed2004

The -4 phenylalanine is required for substrate ubiquitination catalyzed by HECT ubiquitin ligases.

The reaction cycle of HECT domain ubiquitin ligases consists of three steps: 1) binding of an E2 protein, 2) transfer of ubiquitin from E2 to the HECT domain, and 3) transfer of ubiquitin to the substrate. We report the identification of a determinant that is specifically required for the last step of this cycle, a phenylalanine residue located four amino acids from the C terminus of most HECT domains, referred to here as the -4F. Alteration of this residue in human E6AP and Saccharomyces cerevisae Rsp5p did not affect ubiquitin-thioester formation, but effectively blocked substrate ubiquitination. Alteration of the -4F to alanine with concomitant substitution of a nearby residue to phenylalanine only partially restored Rsp5p activity, indicating that precise spatial placement of this residue is important. C-terminally extended E6AP and Rsp5p proteins were also defective for substrate ubiquitination, providing a likely biochemical understanding of a previously isolated Angelman syndrome-associated mutation of E6AP that alters the stop codon of an otherwise wild-type gene. We propose that the -4F may play a role in orienting ubiquitin when it is tethered to the HECT active site cysteine. This may be necessary to allow for approach of the incoming lysine epsilon-amino group of the substrate.

Adaptor Proteins, Signal Transducing↗

PubMed1999

Expression of chicken fibroblast growth factor homologous factor (FHF)-1 and of differentially spliced isoforms of FHF-2 during development and involvement of FHF-2 in chicken limb development.

Members of the fibroblast growth factor (FGF) family have been identified as signaling molecules in a variety of developmental processes, including important roles in limb bud initiation, growth and patterning. This paper reports the cloning and characterization of the chicken orthologues of fibroblast growth factor homologous factors-1 and -2 (cFHF-1/cFGF-12 and cFHF-2/cFGF-13, respectively). We also describe the identification of a novel, conserved isoform of FHF-2 in chickens and mammals. This isoform arises by alternative splicing of the first exon of the FHF-2 gene and is predicted to encode a polypeptide with a distinct amino-terminus. Whole-mount in situ hybridization reveals restricted domains of expression of cFHF-1 and cFHF-2 in the developing neural tube, peripheral sensory ganglia and limb buds, and shows that the two cFHF-2 transcript isoforms are present in non-overlapping spatial distributions in the neural tube and adjacent structures. In the developing limbs, cFHF-1 is confined to the posterior mesoderm in an area that encompasses the zone of polarizing activity and cFHF-2 is confined to the distal anterior mesoderm in a region that largely overlaps the progress zone. Ectopic cFHF-2 expression is induced adjacent to grafts of cells expressing Sonic Hedgehog and the zone of cFHF-2 expression is expanded in talpid2 embryos. In the absence of the apical ectodermal ridge or in wingless or limbless mutant embryos, expression of cFHF-1 and cFHF-2 is lost from the limb bud. A role for cFHF-2 in the patterning and growth of skeletal elements is implied by the observation that engraftment of developing limb buds with QT6 cells expressing a cFHF-2 isoform that is normally expressed in the limb leads to a variety of morphological defects. Finally, we show that a secreted version of cFHF-2 activates the expression of HoxD13, HoxD11, Fgf-4 and BMP-2 ectopically, consistent with cFHF-2 playing a role in anterior-posterior patterning of the limb.

Alternative Splicing↗

PubMed1995

Identification of a spatially specific enhancer element in the chicken Msx-2 gene that regulates its expression in the apical ectodermal ridge of the developing limb buds of transgenic mice.

Msx-2 is a member of the Msx family of homeobox-containing genes expressed in a variety of embryonic tissues involved in epithelial-mesenchymal interactions and pattern formation. In the developing chick limb bud, Msx-2 is expressed in the apical ectodermal ridge, which plays a crucial role in directing the growth and patterning of limb mesoderm. In addition, Msx-2 is expressed in the anterior nonskeletal-forming mesoderm of the limb bud, in the posterior necrotic zone, and in the interdigital mesenchyme. Studies of the altered expression patterns of Msx-2 in amelic and polydactylous mutant chick limbs have suggested that the apical ectodermal ridge and mesodermal domains of Msx-2 expression are independently regulated and that there might be separate cis-regulatory elements in the Msx-2 gene controlling its spatially distinct domains of expression. To test this hypothesis, we have isolated the chicken Msx-2 gene and have tested the ability of various regions of the gene to target expression of LacZ reporter gene to specific regions of the limbs of transgenic mice. A variety of these constructs are consistently expressed only in the apical ectodermal ridge and the ectoderm of the genital tubercle and are not expressed in the mesoderm of the limb bud or in other regions of the embryo where the endogenous Msx-2 gene is expressed. These results suggest the presence of spatially specific cis-regulatory elements in the Msx-2 gene. We identified a 348-bp region in the 5' flanking region of the Msx-2 gene which can act as an apical ectodermal ridge enhancer element when placed in reverse orientation in front of the reporter gene with transcription initiation directed by the minimal hsp68 promoter.

Animals↗

PubMed2000

Emotion recognition deficit in schizophrenia: association with symptomatology and cognition.

BACKGROUND: Previous investigations have found impaired recognition of facial affect in schizophrenia. Controversy exists as to whether this impairment represents a specific emotion recognition deficit when compared with other face recognition control tasks. Regardless of whether the emotion processing deficit is differential, it may uniquely influence other manifestations of schizophrenia. We compared patients and healthy control subjects on computerized tasks of emotion and age recognition. Performances on emotion and age recognition tasks were correlated with cognitive functioning and with symptomatology. METHODS: Thirty-five patients with schizophrenia and 45 healthy people underwent computerized testing for emotion and age recognition. Participants were assessed neuropsychologically, and patients were rated for positive and negative symptoms. RESULTS: The patients with schizophrenia performed worse than control subjects on emotion and age recognition without differential deficit. In both groups, we found higher error rates for identification of emotion in female faces and for identification of sad versus happy faces. In schizophrenic patients, emotion but not age recognition correlated with severity of negative and positive symptoms. In healthy control subjects, neither task correlated with cognitive functions. In schizophrenic patients, emotion but not age recognition correlated with attention, verbal and spatial memory, and language abilities. CONCLUSIONS: This study did not reveal a specific deficit for emotion recognition in schizophrenia; however, our findings lend support to the concept that emotion recognition is uniquely associated in schizophrenia with core symptomatology and cognitive domains.

Adult↗

PubMed2004

New aspects of the alpha-helix to beta-sheet transition in stretched hard alpha-keratin fibers.

The putative transformation of alpha-helices into beta-sheets has been studied for more than 50 years in the case of hard alpha-keratin. In a previous study of stretched keratin fibers, we specified the conditions for beta-sheet appearance within horsehair: the formation of beta-sheets requires at least 30% relative humidity. However, this phenomenon was observed in the whole tissue. Then there was no clear chemical identification of the beta-sheets (keratin or matrix proteins) and the exact location of the beta-sheets across the fiber could not be specified. In this study, using wide-angle x-ray scattering and high spatial resolution infrared microspectroscopy, we could determine and characterize the structural elements across hair sections stretched in water, which provides new information about the aforementioned transition. Our results show that the process can be split into three steps: 1), unraveling of the alpha-helical coiled-coil domains, which starts at roughly 5% macroscopic strain; 2), further transformation of the unraveled coiled-coils into beta-sheet structures, which occurs above roughly 20% macroscopic strain; and 3), spatial expanding of the beta-structured zones from the sample center to its periphery.

Animals↗

PubMed2004

Tbx5 and Tbx4 transcription factors interact with a new chicken PDZ-LIM protein in limb and heart development.

The T-domain transcription factors, Tbx5 and Tbx4, play important roles in vertebrate limb and heart development. To identify interacting and potential Tbx-regulating proteins, we performed a yeast two-hybrid screen with the C-terminal domain of Tbx5 as bait. We identified a new PDZ-LIM protein composed of one N-terminal PDZ and three C-terminal LIM domains, which we named chicken LMP-4. Among the Tbx2, 3, 4, 5 subfamily, we observed exclusive interaction with Tbx5 and Tbx4 proteins. Tbx3 nor Tbx2 can substitute for LMP-4 binding. While chicken LMP-4 associates with Tbx5 or Tbx4, it uses distinct LIM domains to bind to the individual proteins. Subcellular co-localization of LMP-4 and Tbx proteins supports the protein interaction and reveals interference of LMP-4 with Tbx protein distribution, tethering the transcription factors to the cytoskeleton. The protein-protein interaction indicates regulation of Tbx function at the level of transcription factor nuclear localization. During chicken limb and heart development, Tbx5/LMP-4 and Tbx4/LMP-4 are tightly co-expressed in a temporal and spatial manner, suggesting that they operate in the same pathway. Surprisingly, chicken LMP-4 expression domains outside those of Tbx5 in the heart led to the discovery of Tbx4 expression in the outflow tract and the right ventricle of this organ. The Tbx4-expressing cells coincide with those of the recently discovered secondary anterior heart-forming field. The discrete posterior or anterior expression domains in the heart and the exclusive fore- or hindlimb expression of Tbx5 and Tbx4, respectively, suggest common pathways in the heart and limbs. The identification of a new Tbx5/4-specific binding factor further suggests a novel mechanism for Tbx transcription factor regulation in development and disease.

Amino Acid Sequence↗