scholarly journals Ancestral and novel roles of Pax family genes in mollusks

2017 ◽  
Vol 17 (1) ◽  
Author(s):  
Maik Scherholz ◽  
Emanuel Redl ◽  
Tim Wollesen ◽  
André Luiz de Oliveira ◽  
Christiane Todt ◽  
...  
Keyword(s):  
Pax Family

Midline signalling is required for Pax gene regulation and patterning of the eyes

Development ◽  
1995 ◽  
Vol 121 (10) ◽  
pp. 3267-3278 ◽  
Author(s):  
R. Macdonald ◽  
K.A. Barth ◽  
Q. Xu ◽  
N. Holder ◽  
I. Mikkola ◽  
...  
Keyword(s):  
Developmental Stages ◽  
Pigment Epithelium ◽  
Neural Retina ◽  
Protein Distribution ◽  
Optic Stalk ◽  
Retinal Tissue ◽  
Pax6 Protein ◽  
Signalling Molecule ◽  
Pax Family ◽  
In Cells

Pax6 and Pax2 are members of the Pax family of transcription factors that are both expressed in the developing visual system of zebrafish embryos. Pax6 protein is present in all cells that form the neural retina and pigment epithelium, whereas Pax2 is located primarily in cells that will give rise to the optic stalk. In this study, we have addressed the role of midline signalling in the regulation of Pax2 and Pax6 distributions and in the subsequent morphogenesis of the eyes. Midline signalling is severely perturbed in cyclops mutant embryos resulting in an absence of ventral midline CNS tissue and fusion of the eyes. Mutant embryos ectopically express Pax6 in a bridge of tissue around the anterior pole of the neural keel in the position normally occupied by cells that form the optic stalks. In contrast, Pax2 protein is almost completely absent from this region in mutant embryos. Concommitant with the changes in Pax protein distribution, cells in the position of the optic stalks differentiate as retina. These results suggest that a signal emanating from the midline, which is absent in cyclops mutant embryos, may be required to promote Pax2 and inhibit Pax6 expression in cells destined to form the optic stalks. Sonic hedgehog (Shh also known as Vhh-1 and Hhg-1) is a midline signalling molecule that is absent from the neuroepithelium of cyclops mutant embryos at early developmental stages. To test the possibility that Shh might be able to regulate the spatial expression of Pax6 and Pax2 in the optic primordia, it was overexpressed in the developing CNS. The number of cells containing Pax2 was increased following shh overexpression and embryos developed hypertrophied optic stalk-like structures. Complimentary to the changes in Pax2 distribution, there were fewer Pax6-containing cells and pigment epithelium and neural retina were reduced. Our results suggest that Shh or a closely related signalling molecule emanating from midline tissue in the ventral forebrain either directly or indirectly induces the expression of Pax2 and inhibits the expression of Pax6 and thus may regulate the partitioning of the optic primordia into optic stalks and retinal tissue.

PAX2 is expressed in multiple spinal cord interneurons, including a population of EN1+ interneurons that require PAX6 for their development

Development ◽  
1997 ◽  
Vol 124 (22) ◽  
pp. 4493-4503 ◽  
Author(s):  
J.D. Burrill ◽  
L. Moran ◽  
M.D. Goulding ◽  
H. Saueressig
Keyword(s):  
Spinal Cord ◽  
Transcription Factors ◽  
Ventricular Zone ◽  
Cell Types ◽  
Cell Identity ◽  
Patterning Genes ◽  
Postmitotic Neurons ◽  
Pax Family ◽  
Early Activity

Members of the PAX family of transcription factors are candidates for controlling cell identity in the spinal cord. We have morphologically analyzed cells that express one of these transcription factors, PAX2, demonstrating multiple interneuron cell types express PAX2. Two ventral populations of PAX2-expressing interneurons in the spinal cord are marked by coexpression of the transcription factors, EN1 and EVX1. Interestingly, the expression domains of PAX2, EN1 and EVX1 in postmitotic neurons correlate closely with those of Pax6 and Pax7 in the ventricular zone, implicating these patterning genes in the regulation of PAX2, EN1 and EVX1. We show that one of these patterning genes, Pax6, is required for the correct specification of ventral PAX2+ interneurons that coexpress EN1. These results demonstrate that the early activity of patterning genes in the ventricular zone determines interneuron identity in the spinal cord.

scholarly journals Identification of a Portable Repression Domain and an E1A-Responsive Activation Domain in Pax4: a Possible Role of Pax4 as a Transcriptional Repressor in the Pancreas

1999 ◽  
Vol 19 (12) ◽  
pp. 8281-8291 ◽  
Author(s):  
Yoshio Fujitani ◽  
Yoshitaka Kajimoto ◽  
Tetsuyuki Yasuda ◽  
Taka-Aki Matsuoka ◽  
Hideaki Kaneto ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Transcriptional Repressor ◽  
Pancreas Development ◽  
Primary Role ◽  
Transactivation Domain ◽  
Activation Domain ◽  
Pax Family ◽  
Repression Domain

ABSTRACT Pax4 is a paired-domain (PD)-containing transcription factor which plays a crucial role in pancreatic β/δ-cell development. In this study, we characterized the DNA-binding and transactivation properties of mouse Pax4. Repetitive rounds of PCR-based selection led to identification of the optimal DNA-binding sequences for the PD of Pax4. In agreement with the conservation of the optimal binding sequences among the Pax family transcription factors, Pax4 could bind to the potential binding sites for Pax6, another member of the Pax family also involved in endocrine pancreas development. The overexpression of Pax4 in HIT-T15 cells dose dependently inhibited the basal transcriptional activity as well as Pax6-induced activity. Detailed domain mapping analyses using GAL4-Pax4 chimeras revealed that the C-terminal region of Pax4 contains both activation and repression domains. The activation domain was active in the embryonic kidney-derived 293/293T cells and embryonal carcinoma-derived F9 cells, containing adenoviral E1A protein or E1A-like activity, respectively but was inactive or very weakly active in other cells including those of pancreatic β- and α-cell origin. Indeed, the exogenous overexpression of type 13S E1A in heterologous cell types could convert the activation domain to an active one. On the other hand, the repression domain was active regardless of the cell type. When the repression domain was linked to the transactivation domain of a heterologous transcription factor, PDX-1, it could completely abolish the transactivation potential of PDX-1. These observations suggest a primary role of Pax4 as a transcriptional repressor whose function may involve the competitive inhibition of Pax6 function. The identification of the E1A-responsive transactivation domain, however, indicates that the function of Pax4 is subject to posttranslational regulation, providing further support for the complexity of mechanisms that regulate pancreas development.

The Pax protein Noi is required for commissural axon pathway formation in the rostral forebrain

Development ◽  
1997 ◽  
Vol 124 (12) ◽  
pp. 2397-2408 ◽  
Author(s):  
R. Macdonald ◽  
J. Scholes ◽  
U. Strahle ◽  
C. Brennan ◽  
N. Holder ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Glial Cells ◽  
Anterior Commissure ◽  
Optic Tract ◽  
Optic Chiasm ◽  
Commissural Axons ◽  
Optic Axons ◽  
Pathway Formation ◽  
Pax Family ◽  
Choroid Fissure

No-isthmus (Noi) is a member of the zebrafish Pax family of transcriptional regulators that is expressed in restricted domains of the developing CNS. In the developing eye and optic nerve, the Noi+ cells are primitive glial cells that line the choroid fissure and optic stalk/nerve to its junction with the optic tract. This pattern of Noi expression is retained in the adult, defining the optic nerve astroglia, which wrap the left and right nerves separately at the midline, thus forming the bodily crossed optic chiasm found in fish. In embryos carrying mutations in the noi gene, the choroid fissure fails to close, glial cells of the optic nerve fail to differentiate and optic axons exhibit abnormal trajectories exiting the eye and at the midline of the diencephalon. Optic axons select inappropriate pathways into the contralateral optic nerve, rostrally towards the anterior commissure and along the ipsilateral optic tract. Noi+ cells also border the pathway of axons in the postoptic commissure, which is located adjacent to the optic chiasm. These postoptic commissural axons are defasciculated and also exhibit pathfinding defects in noi- embryos. These results indicate that Noi is required in cells that line the pathways taken by optic and non-optic commissural axons for guidance across the midline of the diencephalon. We find that expression of two members of the Netrin family of axon guidance molecules and the signalling protein Sonic hedgehog is disturbed in noi- embryos, whereas several members of the Eph family of receptors and ligands show no obvious alterations in expression at the diencephalic midline.

Sponge Pax cDNA Related to Pax-2/5/8 and Ancient Gene Duplications in the Pax Family

1998 ◽  
Vol 47 (6) ◽  
pp. 640-648 ◽  
Author(s):  
Daisuke Hoshiyama ◽  
Hiroshi Suga ◽  
Naoyuki Iwabe ◽  
Mitsumasa Koyanagi ◽  
Naruo Nikoh ◽  
...  
Keyword(s):  
Gene Duplications ◽  
Pax Family ◽  
Ancient Gene

scholarly journals Systematic alanine scanning of PAX8 paired domain reveals functional importance of the N-subdomain

2019 ◽  
Vol 62 (3) ◽  
pp. 129-135 ◽  
Author(s):  
Megumi Iwahashi ◽  
Satoshi Narumi
Keyword(s):  
Structure Function ◽  
Congenital Hypothyroidism ◽  
Loss Of Function ◽  
Paired Domain ◽  
Functional Importance ◽  
Alanine Scanning Mutagenesis ◽  
Alanine Scanning ◽  
Pathogenicity Prediction ◽  
Pax Family

Thyroid-specific transcription factor PAX8 has an indispensable role in the thyroid gland development, which is evidenced by the facts thatPAX8/Pax8mutations cause congenital hypothyroidism in humans and mice. More than 90% of knownPAX8mutations were located in the paired domain, suggesting the central role of the domain in exerting the molecular function. Structure-function relationships of PAX8, as well as other PAX family transcription factors, have never been investigated in a systematic manner. Here, we conducted the first alanine scanning mutagenesis study, in which 132 alanine variants located in the paired domain of PAX8 were created and systematically evaluatedin vitro. We found that 76 alanine variants (55%) were loss of function (LOF) variants (defined by <30% activity as compared with wild type PAX8). Importantly, the distribution of LOF variants were skewed, with more frequently observed in the N-subdomain (65% of the alanine variants in the N-subdomain) than in the C-subdomain (45%). Twelve out of 13 alanine variants in residues that have been affected in patients with congenital hypothyroidism were actually LOF, suggesting that the alanine scanning data can be used to evaluate the functional importance of mutated residues. Using ourin vitrodata, we tested the accuracy of seven computational algorithms for pathogenicity prediction, showing that they are sensitive but not specific to evaluate on the paired domain alanine variants. Collectively, our experiment-based data would help better understand the structure-function relationships of the paired domain, and would provide a unique resource for pathogenicity prediction of futurePAX8variants.

Pax3 induces cell aggregation and regulates phenotypic mesenchymal-epithelial interconversion

2002 ◽  
Vol 115 (3) ◽  
pp. 517-529 ◽  
Author(s):  
O'Neil Wiggan ◽  
Marc P. Fadel ◽  
Paul A. Hamel
Keyword(s):  
Embryonic Development ◽  
Epithelial To Mesenchymal Transition ◽  
Morphological Changes ◽  
Cell Aggregation ◽  
Structural Defects ◽  
Mesenchymal Transition ◽  
Mammalian Cell Lines ◽  
Morphological Defects ◽  
Pax Family

Paired box-containing transcription factors play fundamental roles in pattern formation during embryonic development of diverse organisms ranging from Drosophila to mammals. Although mutations to Pax3 and other Pax-family genes in both mice and humans result in numerous tissue-specific morphological defects, little is known about the cellular processes that Pax genes regulate. We show that extopic Pax3 expression in two distinct phenotypically mesenchymal mammalian cell lines induces the formation of multi-layered condensed cell aggregates with epithelial characteristics. For one of these lines, we showed further that Pax3-induced cell aggregation is accompanied by specific morphological changes, including a significant reduction in cell size, altered cell shape and dramatic alterations to both membrane and cytoskeleton architecture. In addition to mediating a phenotypic mesenchymal-to-epithelial transition, Pax3 also establishes the conditions in these cells for a subsequent hepatocyte growth factor/scatter factor(HGF/SF)-induced phenotypic epithelial-to-mesenchymal transition. Thus, our data show a novel morphogenetic activity for Pax3 which, when absent in vivo,is predicted to give rise to the observed structural defects in somites and the neural tube during embryonic development.

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