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Hugh S. Taylor - One of the best experts on this subject based on the ideXlab platform.

  • the role of hox genes in female reproductive tract development adult function and fertility
    Cold Spring Harbor Perspectives in Medicine, 2016
    Co-Authors: Hugh S. Taylor
    Abstract:

    HOX genes convey positional identity that leads to the proper partitioning and adult identity of the female reproductive track. Abnormalities in reproductive tract development can be caused by HOX gene mutations or altered HOX gene expression. Diethylstilbestrol (DES) and other endocrine disruptors cause Mullerian defects by changing HOX gene expression. HOX genes are also essential regulators of adult endometrial development. Regulated HOXA10 and HOXA11 expression is necessary for endometrial receptivity; decreased HOXA10 or HOXA11 expression leads to decreased implantation rates. Alternation of HOXA10 and HOXA11 expression has been identified as a mechanism of the decreased implantation associated with endometriosis, polycystic ovarian syndrome, leiomyoma, polyps, adenomyosis, and hydrosalpinx. Alteration of HOX gene expression causes both uterine developmental abnormalities and impaired adult endometrial development that prevent implantation and lead to female infertility.

  • A novel role for the AAA ATPase spastin as a HOXA10 transcriptional corepressor in Ishikawa endometrial cells.
    Molecular endocrinology (Baltimore Md.), 2011
    Co-Authors: Gaurang S. Daftary, Amy M. Tetrault, Elisa M. Jorgensen, Jennifer L. Sarno, Hugh S. Taylor
    Abstract:

    Homeobox A10 (HOXA10), a transcription factor required for uterine development and embryo receptivity, functions downstream of estrogen and progesterone in uterine endometrium. HOXA10 represses endometrial expression of empty spiracles homeobox 2 (EMX2), the human ortholog of Drosophila empty spiracles. The ATPases associated with various cellular activities (AAA) ATPase spastin has a well-characterized role in neurotransmitter trafficking. In this study, we characterize a novel role of spastin in transcriptional regulation. We identified spastin as a novel component of the HOXA10 transcriptional complex in Ishikawa nuclear extracts by immunoprecipitation and mass spectrophotometry. Using EMX2 as a model endometrial HOXA10 target gene, we show that the HOXA10-spastin corepressor complex bound the EMX2 promoter in chromatin immunoprecipitation assays. HOXA10 has been previously shown to repress endometrial EMX2 expression. We further observed that, although cotransfection of HOXA10 and spastin continued to repress endometrial EMX2-luciferase expression, the repression was reversed when spastin small interfering RNA was cotransfected with HOXA10. Mutations in the nuclear localization signal sequences of spastin abrogated not only its nuclear translocation but also its colocalization with HOXA10 as well as reversed EMX2-luciferase repression. Here, we describe a novel role for the AAA ATPase spastin in Ishikawa cells as a HOXA10 corepressor of EMX2. Uterine EMX2 levels are inversely related to embryo implantation rates. HOXA10 acts downstream of progesterone and has been shown to facilitate embryo implantation through regulation of endometrial EMX2 expression. Endometrial spastin, therefore, likely has a novel function downstream of estrogen and progesterone in implantation biology as a cofactor of HOXA10.

  • endometrial polyps affect uterine receptivity
    Fertility and Sterility, 2011
    Co-Authors: Beth W Rackow, Elisa M. Jorgensen, Hugh S. Taylor
    Abstract:

    This case-control study evaluated the effect of hysteroscopically identified endometrial polyps on endometrium by means of HOXA10 and HOXA11, known molecular markers of endometrial receptivity. Uteri with endometrial polyps demonstrated a marked decrease in HOXA10 and HOXA11 messenger RNA levels, which may impair implantation. These findings suggest a molecular mechanism to support the clinical findings of diminished pregnancy rates in women with endometrial polyps.

  • submucosal uterine leiomyomas have a global effect on molecular determinants of endometrial receptivity
    Fertility and Sterility, 2010
    Co-Authors: Beth W Rackow, Hugh S. Taylor
    Abstract:

    Objective To evaluate the effect of uterine leiomyomas on the endometrium using molecular markers of endometrial receptivity: HOXA10 , HOXA11 , LIF , and BTEB1 . Design Case–control study. Setting University medical center. Patient(s) Thirty reproductive-aged women with submucosal, intramural, or no uterine myomas who underwent hysteroscopy or hysterectomy. Intervention(s) Proliferative phase endometrial sampling was performed at the time of surgery. In uteri with a submucosal myoma, directed endometrial biopsies were obtained over the myoma and over normal myometrium. Main Outcome Measure(s) Endometrial HOXA10 expression was evaluated as a primary endpoint using quantitative real-time reverse transcriptase–polymerase chain reaction (RT-PCR) and immunohistochemistry. HOXA11 , BTEB1 , and LIF were evaluated using real-time RT-PCR. Result(s) Endometrial HOXA10 and HOXA11 messenger RNA (mRNA) expression were significantly decreased in uteri with submucosal myomas compared with controls and with uteri with intramural myomas. A similar trend was seen in BTEB1 mRNA expression; however, no difference was found in LIF mRNA expression. Immunohistochemistry localized the decrease in endometrial HOXA10 protein expression to stroma. In the presence of a submucosal myoma, there were no regional differences in gene expression. Conclusion(s) The molecular mechanism by which submucosal myomas adversely affect reproduction includes a global decrease in endometrial HOX gene expression, not simply a focal change over the myoma. This may explain the reproductive dysfunction observed with submucosal myomas.

  • 3 phosphoglycerate dehydrogenase expression is regulated by hoxa10 in murine endometrium and human endometrial cells
    Reproduction, 2010
    Co-Authors: Danielle Vitiello, Jennifer Sarno, Hugh S. Taylor
    Abstract:

    3-Phosphoglycerate dehydrogenase (PHGDH, 3-PGDH) is an enzyme necessary for de novo l-serine biosynthesis. HOXA10 expression is required for endometrial receptivity; however, few target genes of HOXA10 regulation are known. Using a microarray we identified Phgdh as a target of HOXA10 regulation in murine endometrium and confirmed this regulatory relationship in human endometrial cells. PHGDH was downregulated 2.0-fold by HOXA10 and upregulated 4.4-fold by HOXA10 antisense in vivo. In human endometrial cells, real-time PCR results show that pcDNA3.1/HOXA10 transfection decreased PHGDH mRNA expression to 40% of pretreatment level (P<0.05), while PHGDH mRNA expression was increased 2.1-fold (P<0.05) by HOXA10 siRNA. Western blot results confirmed the regulatory relationship in both primary human endometrial stromal and epithelial cells, as well as in human endometrial stromal cells and Ishikawa cells. In human cycling endometrial tissue, immunohistochemical results showed that PHGDH expression is relatively high in the proliferative phase in glandular cells and lower in the secretory phase. Here we report novel expression and regulation of PHGDH in murine and human endometrium. PHGDH is expressed in both endometrial epithelial and stromal cells. HOXA10 represses endometrial PHGDH expression. PHGDH is necessary for serine biosynthesis, which serves as a substrate for protein synthesis. One mechanism by which HOXA10 regulates cellular differentiation may involve limiting protein synthesis in the secretary phase.

Marie Kmita - One of the best experts on this subject based on the ideXlab platform.

  • multifaceted hoxa13 function in urogenital development underlies the hand foot genital syndrome
    Human Molecular Genetics, 2019
    Co-Authors: Marine Roux, Marie Kmita, Maxime Bouchard
    Abstract:

    Hand-Foot-Genital syndrome is a rare condition caused by mutations in the HOXA13 gene and characterized by limb malformations and urogenital defects. While the role of Hoxa13 in limb development has been extensively studied, its function during the development of the urogenital system remains elusive mostly due to the embryonic lethality of Hoxa13 homozygous mutant mice. Using a conditional inactivation strategy, we show that mouse fetuses lacking Hoxa13 function develop megaureters, hydronephrosis and malformations of the uterus, reminiscent of the defects characterizing patients with Hand-Foot-Genital syndrome. Our analysis reveals that Hoxa13 plays a critical role in Mullerian ducts fusion and in ureter remodeling by regulating the elimination of the caudal common nephric duct, eventually preventing the separation from the nephric duct. Our data also reveal a specific role for Hoxa13 in the urogenital sinus, which is in part mediated by Gata3, as well as Hoxa13 requirement for the proper organization of the ureter. Finally, we provide evidence that Hoxa13 provides positional and temporal cues during the development of the lower urogenital system, a sine qua non condition for the proper function of the urinary system.

  • evolution of HOXA11 regulation in vertebrates is linked to the pentadactyl state
    Nature, 2016
    Co-Authors: Yacine Kherdjemil, Scott H Stadler, Kyriel M Pineault, Deneen M Wellik, Robert L Lalonde, Rushikesh Sheth, Annie Dumouchel, Gemma De Martino, Marie Andri E Akimenko, Marie Kmita
    Abstract:

    The fin-to-limb transition represents one of the major vertebrate morphological innovations associated with the transition from aquatic to terrestrial life and is an attractive model for gaining insights into the mechanisms of morphological diversity between species. One of the characteristic features of limbs is the presence of digits at their extremities. Although most tetrapods have limbs with five digits (pentadactyl limbs), palaeontological data indicate that digits emerged in lobed fins of early tetrapods, which were polydactylous. How the transition to pentadactyl limbs occurred remains unclear. Here we show that the mutually exclusive expression of the mouse genes HOXA11 and Hoxa13, which were previously proposed to be involved in the origin of the tetrapod limb, is required for the pentadactyl state. We further demonstrate that the exclusion of HOXA11 from the Hoxa13 domain relies on an enhancer that drives antisense transcription at the HOXA11 locus after activation by HOXA13 and HOXD13. Finally, we show that the enhancer that drives antisense transcription of the mouse HOXA11 gene is absent in zebrafish, which, together with the largely overlapping expression of HOXA11 and hoxa13 genes reported in fish, suggests that this enhancer emerged in the course of the fin-to-limb transition. On the basis of the polydactyly that we observed after expression of HOXA11 in distal limbs, we propose that the evolution of HOXA11 regulation contributed to the transition from polydactyl limbs in stem-group tetrapods to pentadactyl limbs in extant tetrapods.

  • recruitment of 5 hoxa genes in the allantois is essential for proper extra embryonic function in placental mammals
    Development, 2012
    Co-Authors: Martina Scotti, Marie Kmita
    Abstract:

    The Hox gene family is well known for its functions in establishing morphological diversity along the anterior-posterior axis of developing embryos. In mammals, one of these genes, Hoxa13, is crucial for embryonic survival, as its function is required for the proper expansion of the fetal vasculature in the placenta. Thus, it appears that the developmental strategy specific to placental mammals is linked, at least in part, to the recruitment of Hoxa13 function in developing extra-embryonic tissues. Yet, the mechanism underlying this extra-embryonic recruitment is unknown. Here, we provide evidence that this functional novelty is not exclusive to Hoxa13 but is shared with its neighboring HOXA11 and Hoxa10 genes. We show that the extra-embryonic function of these three Hoxa genes stems from their specific expression in the allantois, an extra-embryonic hallmark of amniote vertebrates. Interestingly, Hoxa10-13 expression in the allantois is conserved in chick embryos, which are non-placental amniotes, suggesting that the extra-embryonic recruitment of Hoxa10, HOXA11 and Hoxa13 most likely arose in amniotes, i.e. prior to the emergence of placental mammals. Finally, using a series of targeted recombination and transgenic assays, we provide evidence that the regulatory mechanism underlying Hoxa expression in the allantois is extremely complex and relies on several cis-regulatory sequences.

Karen D. Crow - One of the best experts on this subject based on the ideXlab platform.

  • The role of HOXA11 and HoxA13 in the evolution of novel fin morphologies in a representative batoid (Leucoraja erinacea)
    EvoDevo, 2017
    Co-Authors: Shannon N. Barry, Karen D. Crow
    Abstract:

    BackgroundBatoids exhibit unique body plans with derived fin morphologies, such as the anteriorly expanded pectoral fins that fuse to the head, or distally extended anterior pelvic fin lobes used for a modified swimming technique utilized by skates (Rajidae). The little skate (Leucoraja erinacea), exhibits both of these unique fin morphologies. These fin modifications are not present in a typical shark body plan, and little is known regarding the mechanisms underlying their development. A recent study identified a novel apical ectodermal ridge (AER) associated with the development of the anterior pectoral fin in the little skate, but the role of the posterior HoxA genes was not featured during skate fin development.ResultsWe present the first evidence for HoxA expression (HOXA11 and HoxA13) in novel AER domains associated with the development of three novel fin morphologies in a representative batoid, L. erinacea. We found HoxA13 expression associated with the recently described novel AER in the anterior pectoral fin, and HOXA11 expression in a novel AER domain in the anterior pelvic fin that we describe here. We find that both HOXA11 and HoxA13 are expressed in claspers, and while HOXA11 is expressed in pelvic fins and claspers, HoxA13 is expressed exclusively in developing claspers of males. Finally, HOXA11 expression is associated with the developing fin rays in paired fins.ConclusionOverall, these results indicate that the posterior HoxA genes play an important role in the morphological evolution of paired fins in a representative batoid. These data suggest that the batoids utilize a unique Hox code, where the posterior HoxA genes exhibit distinct expression patterns that are likely associated with specification of novel fin morphologies.

  • the role of HOXA11 and hoxa13 in the evolution of novel fin morphologies in a representative batoid leucoraja erinacea
    Evodevo, 2017
    Co-Authors: Shannon N. Barry, Karen D. Crow
    Abstract:

    Batoids exhibit unique body plans with derived fin morphologies, such as the anteriorly expanded pectoral fins that fuse to the head, or distally extended anterior pelvic fin lobes used for a modified swimming technique utilized by skates (Rajidae). The little skate (Leucoraja erinacea), exhibits both of these unique fin morphologies. These fin modifications are not present in a typical shark body plan, and little is known regarding the mechanisms underlying their development. A recent study identified a novel apical ectodermal ridge (AER) associated with the development of the anterior pectoral fin in the little skate, but the role of the posterior HoxA genes was not featured during skate fin development. We present the first evidence for HoxA expression (HOXA11 and HoxA13) in novel AER domains associated with the development of three novel fin morphologies in a representative batoid, L. erinacea. We found HoxA13 expression associated with the recently described novel AER in the anterior pectoral fin, and HOXA11 expression in a novel AER domain in the anterior pelvic fin that we describe here. We find that both HOXA11 and HoxA13 are expressed in claspers, and while HOXA11 is expressed in pelvic fins and claspers, HoxA13 is expressed exclusively in developing claspers of males. Finally, HOXA11 expression is associated with the developing fin rays in paired fins. Overall, these results indicate that the posterior HoxA genes play an important role in the morphological evolution of paired fins in a representative batoid. These data suggest that the batoids utilize a unique Hox code, where the posterior HoxA genes exhibit distinct expression patterns that are likely associated with specification of novel fin morphologies.

Shannon N. Barry - One of the best experts on this subject based on the ideXlab platform.

  • The role of HOXA11 and HoxA13 in the evolution of novel fin morphologies in a representative batoid (Leucoraja erinacea)
    EvoDevo, 2017
    Co-Authors: Shannon N. Barry, Karen D. Crow
    Abstract:

    BackgroundBatoids exhibit unique body plans with derived fin morphologies, such as the anteriorly expanded pectoral fins that fuse to the head, or distally extended anterior pelvic fin lobes used for a modified swimming technique utilized by skates (Rajidae). The little skate (Leucoraja erinacea), exhibits both of these unique fin morphologies. These fin modifications are not present in a typical shark body plan, and little is known regarding the mechanisms underlying their development. A recent study identified a novel apical ectodermal ridge (AER) associated with the development of the anterior pectoral fin in the little skate, but the role of the posterior HoxA genes was not featured during skate fin development.ResultsWe present the first evidence for HoxA expression (HOXA11 and HoxA13) in novel AER domains associated with the development of three novel fin morphologies in a representative batoid, L. erinacea. We found HoxA13 expression associated with the recently described novel AER in the anterior pectoral fin, and HOXA11 expression in a novel AER domain in the anterior pelvic fin that we describe here. We find that both HOXA11 and HoxA13 are expressed in claspers, and while HOXA11 is expressed in pelvic fins and claspers, HoxA13 is expressed exclusively in developing claspers of males. Finally, HOXA11 expression is associated with the developing fin rays in paired fins.ConclusionOverall, these results indicate that the posterior HoxA genes play an important role in the morphological evolution of paired fins in a representative batoid. These data suggest that the batoids utilize a unique Hox code, where the posterior HoxA genes exhibit distinct expression patterns that are likely associated with specification of novel fin morphologies.

  • the role of HOXA11 and hoxa13 in the evolution of novel fin morphologies in a representative batoid leucoraja erinacea
    Evodevo, 2017
    Co-Authors: Shannon N. Barry, Karen D. Crow
    Abstract:

    Batoids exhibit unique body plans with derived fin morphologies, such as the anteriorly expanded pectoral fins that fuse to the head, or distally extended anterior pelvic fin lobes used for a modified swimming technique utilized by skates (Rajidae). The little skate (Leucoraja erinacea), exhibits both of these unique fin morphologies. These fin modifications are not present in a typical shark body plan, and little is known regarding the mechanisms underlying their development. A recent study identified a novel apical ectodermal ridge (AER) associated with the development of the anterior pectoral fin in the little skate, but the role of the posterior HoxA genes was not featured during skate fin development. We present the first evidence for HoxA expression (HOXA11 and HoxA13) in novel AER domains associated with the development of three novel fin morphologies in a representative batoid, L. erinacea. We found HoxA13 expression associated with the recently described novel AER in the anterior pectoral fin, and HOXA11 expression in a novel AER domain in the anterior pelvic fin that we describe here. We find that both HOXA11 and HoxA13 are expressed in claspers, and while HOXA11 is expressed in pelvic fins and claspers, HoxA13 is expressed exclusively in developing claspers of males. Finally, HOXA11 expression is associated with the developing fin rays in paired fins. Overall, these results indicate that the posterior HoxA genes play an important role in the morphological evolution of paired fins in a representative batoid. These data suggest that the batoids utilize a unique Hox code, where the posterior HoxA genes exhibit distinct expression patterns that are likely associated with specification of novel fin morphologies.

Paolo Sordino - One of the best experts on this subject based on the ideXlab platform.

  • Expression of meis and HOXA11 in dipnoan and teleost fins provides new insights into the evolution of vertebrate appendages
    EvoDevo, 2018
    Co-Authors: Fernanda Langellotto, Maria Fiorentino, Elena Felice, Luigi Caputi, Valeria Nittoli, Jean M. P. Joss, Paolo Sordino
    Abstract:

    Background The concerted activity of Meis and HOXA11 transcription factors is essential for the subdivision of tetrapod limbs into proximo-distal (PD) domains; however, little is know about the evolution of this patterning mechanism. Here, we aim to study the expression of meis and HOXA11 orthologues in the median and paired rayed fins of zebrafish and in the lobed fins of the Australian lungfish. Results First, a late phase of expression of meis1.1 and HOXA11b in zebrafish dorsal and anal fins relates with segmentation of endochondral elements in proximal and distal radials. Second, our zebrafish in situ hybridization results reveal spatial and temporal changes between pectoral and pelvic fins. Third, in situ analysis of meis1 , meis3 and HOXA11 genes in Neoceratodus pectoral fins identifies decoupled domains of expression along the PD axis. Conclusions Our data raise the possibility that the origin of stylopod and zeugopod lies much deeper in gnathostome evolution and that variation in meis and HOXA11 expression has played a substantial role in the transformation of appendage anatomy. Moreover, these observations provide evidence that the Meis / HOXA11 profile considered a hallmark of stylopod/zeugopod patterning is present in Neoceratodus .

  • expression of meis and HOXA11 in dipnoan and teleost fins provides new insights into the evolution of vertebrate appendages
    Evodevo, 2018
    Co-Authors: Fernanda Langellotto, Maria Fiorentino, Elena Felice, Luigi Caputi, Valeria Nittoli, Jean M. P. Joss, Paolo Sordino
    Abstract:

    The concerted activity of Meis and HOXA11 transcription factors is essential for the subdivision of tetrapod limbs into proximo-distal (PD) domains; however, little is know about the evolution of this patterning mechanism. Here, we aim to study the expression of meis and HOXA11 orthologues in the median and paired rayed fins of zebrafish and in the lobed fins of the Australian lungfish. First, a late phase of expression of meis1.1 and HOXA11b in zebrafish dorsal and anal fins relates with segmentation of endochondral elements in proximal and distal radials. Second, our zebrafish in situ hybridization results reveal spatial and temporal changes between pectoral and pelvic fins. Third, in situ analysis of meis1, meis3 and HOXA11 genes in Neoceratodus pectoral fins identifies decoupled domains of expression along the PD axis. Our data raise the possibility that the origin of stylopod and zeugopod lies much deeper in gnathostome evolution and that variation in meis and HOXA11 expression has played a substantial role in the transformation of appendage anatomy. Moreover, these observations provide evidence that the Meis/HOXA11 profile considered a hallmark of stylopod/zeugopod patterning is present in Neoceratodus.

  • MOESM5 of Expression of meis and HOXA11 in dipnoan and teleost fins provides new insights into the evolution of vertebrate appendages
    2018
    Co-Authors: Fernanda Langellotto, Maria Fiorentino, Elena Felice, Luigi Caputi, Valeria Nittoli, Jean M. P. Joss, Paolo Sordino
    Abstract:

    Additional file 5: Fig. 5 HOXA11 expression in lungfish. In situ results in nervous system, tail and digestive tract