Comparative analysis of Prx1 and Prx2 expression in mice provides evidence for incomplete compensation

Chesterman, Elizabeth S.; Kern, Michael J.

doi:10.1002/ar.10028

Cited by 14 publications

(7 citation statements)

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“…Prx1 is expressed in the limb bud in mesenchyme surrounding the prechondrogenic condensations and the perichondrium and periosteum (Kern et al, 1992;Leussink et al, 1995;Nohno et al, 1993). A Prx1 antibody, directed against a region common to the two isoforms revealed that Prx1 protein expression is in agreement with the previously reported in situ hybridization results in the developing limb of both mouse and chicken (Chesterman and Kern, 2002, and data not shown). Prx1Ϫ/Ϫ mice have perinatal lethality with significant craniofacial and limb deformities (Martin et al, 1995).…”

Section: Introductionsupporting

confidence: 90%

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Opposing roles of two isoforms of the Prx1 homeobox gene in chondrogenesis

Peterson

Hoffman

Kern

2005

Developmental Dynamics

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The Prx1 homeobox gene is critical for cartilage and bone development as suggested by previous expression studies and demonstrated by gene targeting. However, neither approach assessed the individual roles of the two isoforms Prx1a and Prx1b. In this study, Western blot analysis demonstrates that, in the early stages of chondrogenesis, during mesenchymal condensation, only Prx1a is expressed. Higher level Prx1b expression is concomitant with the formation of a defined perichondrium. Prx1a overexpression in limb micro mass cultures results in an increase in the number of prechondrogenic condensations and cartilage nodules, whereas overexpression of Prx1b results in a decrease. Prx1a increases the percentage of proliferating cells in micro mass cultures and decreases apoptosis. The Prx1b isoform does not alter proliferation, but it does increase apoptosis, which is opposite of Prx1a. These results suggest that the Prx1a:Prx1b ratio and the alternative splicing mechanism that generates these two isoforms are critical in controlling chondrogenesis. Developmental Dynamics 233:811-821, 2005.

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Section: Introductionsupporting

confidence: 90%

“…The anti-Prx1 antibody has been shown to recognize Prx1 proteins in chick, mouse, and human tissues (Chesterman et al, 2001;Chesterman and Kern, 2002). The TN-C polyclonal antibody used in this study was prepared against chicken TN-C and isolated as previously described (Hoff-man et al, 1988).…”

Section: Immunodetection Of Limb Micro Mass Culturesmentioning

confidence: 99%

Opposing roles of two isoforms of the Prx1 homeobox gene in chondrogenesis

Peterson

Hoffman

Kern

2005

Developmental Dynamics

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“…In the absence of this cofactor, the OAR domain masks the activation domain and reduces the affinity of prx1a for DNA binding sites. When bound by its co-factor, the activation domain becomes unmasked and the DNA binding affinity increases [76,77,81]. In the case of Nematostella rx , the situation may be somewhat simpler than in the mouse prx1 gene, because except for the presence or absence of the OAR domain itself, the alternative splice variants encode essentially identical proteins.…”

Section: Discussionmentioning

confidence: 99%

A conserved cluster of three PRD-class homeobox genes (homeobrain, rx and orthopedia) in the Cnidaria and Protostomia

Mazza

Pang

Reitzel

et al. 2010

EvoDevo

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Background: Homeobox genes are a superclass of transcription factors with diverse developmental regulatory functions, which are found in plants, fungi and animals. In animals, several Antennapedia (ANTP)-class homeobox genes reside in extremely ancient gene clusters (for example, the Hox, ParaHox, and NKL clusters) and the evolution of these clusters has been implicated in the morphological diversification of animal bodyplans. By contrast, similarly ancient gene clusters have not been reported among the other classes of homeobox genes (that is, the LIM, POU, PRD and SIX classes).Results: Using a combination of in silico queries and phylogenetic analyses, we found that a cluster of three PRD-class homeobox genes (Homeobrain (hbn), Rax (rx) and Orthopedia (otp)) is present in cnidarians, insects and mollusks (a partial cluster comprising hbn and rx is present in the placozoan Trichoplax adhaerens). We failed to identify this 'HRO' cluster in deuterostomes; in fact, the Homeobrain gene appears to be missing from the chordate genomes we examined, although it is present in hemichordates and echinoderms. To illuminate the ancestral organization and function of this ancient cluster, we mapped the constituent genes against the assembled genome of a model cnidarian, the sea anemone Nematostella vectensis, and characterized their spatiotemporal expression using in situ hybridization. In N. vectensis, these genes reside in a span of 33 kb with the same gene order as previously reported in insects. Comparisons of genomic sequences and expressed sequence tags revealed the presence of alternative transcripts of Nv-otp and two highly unusual protein-coding polymorphisms in the terminal helix of the Nv-rx homeodomain. A population genetic survey revealed the Rx polymorphisms to be widespread in natural populations. During larval development, all three genes are expressed in the ectoderm, in non-overlapping territories along the oral-aboral axis, with distinct temporal expression. Conclusion:We report the first evidence for a PRD-class homeobox cluster that appears to have been conserved since the time of the cnidarian-bilaterian ancestor, and possibly even earlier, given the presence of a partial cluster in the placozoan Trichoplax. Very similar clusters comprising these three genes exist in Nematostella and diverse protostomes. Interestingly, in chordates, one member of the ancestral cluster (homeobrain) has apparently been lost, and there is no linkage between rx and orthopedia in any of the vertebrates. In Nematostella, the spatial expression of these three genes along the body column is not colinear with their physical order in the cluster but the temporal expression is, therefore, using the terminology that has been applied to the Hox cluster genes, the HRO cluster would appear to exhibit temporal but not spatial colinearity. It remains to be seen whether the mechanisms responsible for the evolutionary conservation of the HRO cluster are the same mechanisms responsible for cohesion of the Hox cluster and other ANT...

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“…Another closely related protein, Prx1, plays roles in development of the heart and forebrain [42] and of the bone in the skull, limbs and vertebral column as revealed in loss-of-function cases [43]. Prx2 and Prx1 are expressed in very similar patterns, predominantly in the mesenchyme [44], and are important for correct skeletogenesis with overlapping expression in limited tissues [45].…”

Section: Discussionmentioning

confidence: 99%

Molecular Cloning of Paired Related Homeobox 2 (Prx2) as a Novel Pituitary Transcription Factor

Sugiyama

Ishikawa

Katō

et al. 2009

Journal of Reproduction and Development

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Abstract. This study aimed to identify protein(s) that bind(s) to the highly AT-rich sequence of porcine Fshb promoter region -852/-746 (named Fd2) by the Yeast One-Hybrid Cloning System and finally a paired related homeodomain transcription factor, Prx2, known as a key factor for skeletogenesis was cloned. RT-PCR analysis of fetal and postnatal porcine pituitaries demonstrated that Prx2 starts to be expressed at around fetal days 40-50 just before the beginning of Lhb-expression and that the level of Prx2 increases after birth. Immunohistochemical analysis of the prepubertal porcine pituitary revealed that some Prx2-positive cells overlap some Lhβ-positive cells. Transient transfection assay using nonpituitary CHO cells and pituitary tumor-derived LβT2 cells revealed that Prx2 plays a cell-type dependent role in modulation of the Fshb promoter, showing stimulation in CHO cells and repression in LβT2 cells via the regions of Fd2 and -596/-239. The binding ability of Prx2 to the regions of Fd2 and -596/-239 was confirmed by electrophoretic mobility shift assay. DNase I footprinting revealed that broad regions of Fd2 were bound by Prx2 and that -596/-239 contained seven Prx2-binding sites. The SELEX method using a random N15-mer oligonucleotide pool demonstrated that Prx2 monomer binds to a TAATT motif, which is present in Fd2 and -596/-239. However, the binding of Prx2 to TAATT with a single molecule and its inverted repeat with two molecules could not induce transcriptional activation, indicating that the Prx2-dependent transcriptional modulation demonstrated in cultured cells is not introduced by Prx2 alone. Thus, this study demonstrated for the first time that Prx2 is expressed in the pituitary gland and at least in a part of gonadotropes in which Prx2 may play a role in repression of the Fshb gene. Key words: Follicle-stimulating hormone (FSH), Gonadotropin, Pituitary, Prx2, Transcription factor (J. Reprod. Dev. 55: [502][503][504][505][506][507][508][509][510][511] 2009) ollicle-stimulating hormone (FSH), in addition to luteinizing hormone (LH) and thyroid-stimulating hormone (TSH), is a member of the pituitary glycoprotein hormone family consisting of a common α subunit (αGSU) and a noncovalently associated hormone-specific β subunit and plays crucial roles in folliculogenesis in females and spermatogenesis in males. Notably, three gonadotropin subunit genes, Cga, Fshb and Lhb, are expressed in the same pituitary cell, the gonadotrope. Several investigations have been conducted to clarify the specific regulatory mechanism of Cga and two β subunit genes (reviewed in Refs. [1] We have previously observed that plural nuclear proteins specifically bind to the AT-rich sequence of the porcine Fshb promoter region -852/-746 (named Fd2) [10], and have demonstrated that the upstream region -852/+10 containing Fd2 is sufficient for gonadotrope-specific expression [11]. Cloning by the Yeast OneHybrid System using Fd2 as a bait sequence led us to select plural proteins including Prop1 and Lhx2 [12,13]. At the same t...

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Comparative analysis of Prx1 and Prx2 expression in mice provides evidence for incomplete compensation

Cited by 14 publications

References 12 publications

Opposing roles of two isoforms of the Prx1 homeobox gene in chondrogenesis

Opposing roles of two isoforms of the Prx1 homeobox gene in chondrogenesis

A conserved cluster of three PRD-class homeobox genes (homeobrain, rx and orthopedia) in the Cnidaria and Protostomia

Molecular Cloning of Paired Related Homeobox 2 (Prx2) as a Novel Pituitary Transcription Factor

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