scholarly journals Bmp7 and Lef1 Are the Downstream Effectors of Androgen Signaling in Androgen-Induced Sex Characteristics Development in Medaka

Endocrinology ◽  
2014 ◽  
Vol 155 (2) ◽  
pp. 449-462 ◽  
Author(s):  
Yukiko Ogino ◽  
Ikumi Hirakawa ◽  
Keiji Inohaya ◽  
Eri Sumiya ◽  
Shinichi Miyagawa ◽  
...  

Androgens play key roles in the morphological specification of male type sex attractive and reproductive organs, whereas little is known about the developmental mechanisms of such secondary sex characters. Medaka offers a clue about sexual differentiation. They show a prominent masculine sexual character for appendage development, the formation of papillary processes in the anal fin, which has been induced in females by exogenous androgen exposure. This current study shows that the development of papillary processes is promoted by androgen-dependent augmentation of bone morphogenic protein 7 (Bmp7) and lymphoid enhancer-binding factor-1 (Lef1). Androgen receptor (AR) subtypes, ARα and ARβ, are expressed in the distal region of outgrowing bone nodules of developing papillary processes. Development of papillary processes concomitant with the induction of Bmp7 and Lef1 in the distal bone nodules by exposure to methyltestosterone was significantly suppressed by an antiandrogen, flutamide, in female medaka. When Bmp signaling was inhibited in methyltestosterone-exposed females by its inhibitor, dorsomorphin, Lef1 expression was suppressed accompanied by reduced proliferation in the distal bone nodules and retarded bone deposition. These observations indicate that androgen-dependent expressions of Bmp7 and Lef1 are required for the bone nodule outgrowth leading to the formation of these secondary sex characteristics in medaka. The formation of androgen-induced papillary processes may provide insights into the mechanisms regulating the specification of sexual features in vertebrates.

Andrologia ◽  
2009 ◽  
Vol 23 (6) ◽  
pp. 435-437 ◽  
Author(s):  
Z. G. Liang ◽  
M. Kamada ◽  
S. M. Mitsudo ◽  
S. S. Koide

2011 ◽  
Vol 49 (No. 12) ◽  
pp. 511-516
Author(s):  
P. Trefil ◽  
A. Mičáková ◽  
J. Mucksová ◽  
M. Poplštein ◽  
Brillard J-P ◽  
...  

The objectives of this study were to assess post-hatch development of chickens treated in ovo with the aromatase inhibitor YM511. A total of 137 eggs coming from artificially inseminated hens were at first injected in the albumen with either DMSO alone (54 eggs injected, control group) or with DMSO + aromatase inhibitor (YM511, 1 mg/egg, 83 eggs injected, treated group) and then incubated under standard conditions. Out of the 24 chicks hatched in the treated group, 16 were genetic males (ZZ) and 8 were genetic females (ZW). By 26 weeks of age, secondary sex characteristics of females (cloaca, comb, wattles, song, feathers of hackle and tail) progressively transformed into a male phenotype. Using CT-scanner technology in these 8 birds, the presence of irregular testis-like masses positioned in the antero-ventral portion of the kidneys was observable, an indication that reproductive organs had also been affected by the treatment.    


Development ◽  
1996 ◽  
Vol 122 (11) ◽  
pp. 3557-3566 ◽  
Author(s):  
Y. Kawakami ◽  
T. Ishikawa ◽  
M. Shimabara ◽  
N. Tanda ◽  
M. Enomoto-Iwamoto ◽  
...  

To examine the role of BMP signaling during limb pattern formation, we isolated chicken cDNAs encoding type I (BRK-1 and BRK-2) and type II (BRK-3) receptors for bone morphogenetic proteins. BRK-2 and BRK-3, which constitute dual-affinity signaling receptor complexes for BMPs, are co-expressed in condensing precartilaginous cells, while BRK-1 is weakly expressed in the limb mesenchyme. BRK-3 is also expressed in the apical ectodermal ridge and interdigital limb mesenchyme. BRK-2 is intensely expressed in the posterior-distal region of the limb bud. During digit duplication by implanting Sonic hedgehog-producing cells, BRK-2 expression is induced anteriorly in the new digit forming region as observed for BMP-2 and BMP-7 expression in the limb bud. Dominant-negative effects on BMP signaling were obtained by over-expressing kinase domain-deficient forms of the receptors. Chondrogenesis of limb mesenchymal cells is markedly inhibited by dominant-negative BRK-2 and BRK-3, but not by BRK-1. Although the bone pattern was not disturbed by expressing individual dominant-negative BRK independently, preferential distal and posterior limb truncations resulted from co-expressing the dominant-negative forms of BRK-2 and BRK-3 in the whole limb bud, thus providing evidence that BMPs are essential morphogenetic signals for limb bone patterning.


2014 ◽  
Vol 206 (5) ◽  
pp. 671-688 ◽  
Author(s):  
Laura Corrigan ◽  
Siamak Redhai ◽  
Aaron Leiblich ◽  
Shih-Jung Fan ◽  
Sumeth M.W. Perera ◽  
...  

Male reproductive glands secrete signals into seminal fluid to facilitate reproductive success. In Drosophila melanogaster, these signals are generated by a variety of seminal peptides, many produced by the accessory glands (AGs). One epithelial cell type in the adult male AGs, the secondary cell (SC), grows selectively in response to bone morphogenetic protein (BMP) signaling. This signaling is involved in blocking the rapid remating of mated females, which contributes to the reproductive advantage of the first male to mate. In this paper, we show that SCs secrete exosomes, membrane-bound vesicles generated inside late endosomal multivesicular bodies (MVBs). After mating, exosomes fuse with sperm (as also seen in vitro for human prostate-derived exosomes and sperm) and interact with female reproductive tract epithelia. Exosome release was required to inhibit female remating behavior, suggesting that exosomes are downstream effectors of BMP signaling. Indeed, when BMP signaling was reduced in SCs, vesicles were still formed in MVBs but not secreted as exosomes. These results demonstrate a new function for the MVB–exosome pathway in the reproductive tract that appears to be conserved across evolution.


1991 ◽  
Vol 11 (1) ◽  
pp. 523-532
Author(s):  
P Georgel ◽  
P Ramain ◽  
A Giangrande ◽  
G Dretzen ◽  
G Richards ◽  
...  

The transcription of the Drosophila melanogaster 68C salivary gland glue gene Sgs-3 involves the interaction of a distal and a proximal regulatory region. These are marked in vivo by a specific chromatin structure which is established sequentially during development, starting early in embryogenesis. The distal region is characterized by a stage- and tissue-specific DNase I hypersensitive site. A stage- and tissue-specific factor, GEBF-I, binds in this region and is missing in 2B5 mutant larvae which lack Sgs-3 transcripts. This binding involves the simultaneous interaction with two distinct DNA sequences which induces conformational changes in the protein. Salivary glands acquire competence to respond to ecdysone in the mid-third larval instar, whereafter the hormone rapidly induces both the GEBF-I protein and Sgs-3 transcription.


Reproduction ◽  
2011 ◽  
Vol 142 (4) ◽  
pp. 573-579 ◽  
Author(s):  
Pradeep S Tanwar ◽  
James R McFarlane

Various members of the bone morphogenetic protein (BMP) family have been shown to regulate mammalian follicular development by affecting granulosa cell proliferation and steroidogenesis.In situhybridization studies have shown expression of BMPR1A, BMPR1B, and BMPR2 in the granulosa cells and oocyte of most of the follicles in the ovary, suggesting that these cells have the capacity to respond to BMP signaling. Although much is known about BMP4 signaling, its expression pattern in the female reproductive tract (FRT) is still unclear. The objective of the current study was to characterize the expression of BMP4 and its downstream target proteins (pSMAD1/5/8) in the FRT. In the ovary, BMP4 protein was detected in all the stages of follicular development. Staining for pSMAD1/5/8 was observed in granulosa cells and oocytes of all the stages of follicular development including primordial follicles, suggesting that these follicles are responsive to autocrine/paracrine BMP signaling. In the uterus, BMP4 and pSMAD1/5/8 staining was observed in all three compartments and strongest expression was observed during the estrus phase. BMP4- and pSMAD1/5/8-specific staining was also observed in oviductal epithelium. Different forms (apparent MW: 50, 35, and 15 kDa) of BMP4 were detected in mouse ovary by western blot analysis. In conclusion, these results have defined BMP4 and pSMAD1/5/8 protein expression in the mouse FRT and highlighted the importance of BMP4 in folliculogenesis.


2013 ◽  
Vol 305 (4) ◽  
pp. L312-L321 ◽  
Author(s):  
Jun Yang ◽  
Xiaohui Li ◽  
Ying Li ◽  
Mark Southwood ◽  
Lingying Ye ◽  
...  

Bone morphogenetic protein type II receptor (BMPR-II) mutations are responsible for over 70% of cases of heritable pulmonary arterial hypertension (PAH). Loss of BMP signaling promotes pulmonary vascular remodeling via modulation of pulmonary artery smooth muscle cell (PASMC) proliferation. Id proteins (Id1–4) are major downstream transcriptional targets of BMP signaling. However, the impact of BMPR-II mutation on the expression of the range of Id proteins and the contribution of individual Id proteins to abnormal PASMC function remain unclear. Human PASMCs were used to determine the expression of Id proteins (Id1–4) by real-time PCR and immunoblotting. The BMP responses in control cells were compared with PASMCs harboring BMPR-II mutations and cells in which BMPR-II was knocked down by siRNA transfection. Id3 expression in pulmonary vessels was also investigated in BMPR-II mutant mice and in patients with heritable PAH. BMP4 and BMP6, but not BMP9, induced mRNA expression of Id1, Id2, and Id3. The BMP-stimulated induction of Id1 and Id3 was markedly reduced in BMPR-II mutant PASMCs and in control PASMCs following siRNA silencing of BMPR-II. Pulmonary arteries in BMPR-II mutant mice and patients with heritable PAH demonstrated reduced levels of Id3 compared with control subjects. Lentiviral overexpression of Id3 reduced cell cycle progression and inhibited proliferation of PASMCs. Lipopolysaccharide further reduced Id3 expression in mutant PASMCs. In conclusion, Id proteins, and particularly Id1 and Id3, are critical downstream effectors of BMP signaling in PASMCs. Loss of BMPR-II function reduces the induction of Id genes in PASMCs, Id1, and Id3 regulate the proliferation of PASMCs via cell cycle inhibition, an effect that may be exacerbated by inflammatory stimuli.


2017 ◽  
Author(s):  
Uday Madaan ◽  
Edlira Yzeiraj ◽  
Michael Meade ◽  
Christine A. Rushlow ◽  
Cathy Savage-Dunn

AbstractBody size is a tightly regulated phenotype in metazoans that is dependent on both intrinsic and extrinsic factors. While signaling pathways such as insulin, Hippo, and myostatin are known to control organ and body size, the downstream effectors that mediate their effects are still poorly understood. In the nematode C. elegans, a Bone Morphogenetic Protein (BMP)-related signaling pathway is the major regulator of growth and body size. DBL-1, the BMP-related ligand, is secreted by neurons and body wall muscle, and acts as a dose-dependent regulator of body size. We investigated the transcriptional network through which the DBL-1/BMP pathway regulates body size and identified cuticle collagen genes as major effectors of growth control. Here we demonstrate that cuticle collagen genes can act as positive regulators (col-41), dose-sensitive regulators (rol-6), and negative regulators (col-141, col-142) of body size. Moreover, we show requirement of DBL-1/BMP signaling for stage-specific expression of cuticle collagen genes. We used chromatin immunoprecipitation followed by high throughput sequencing (ChIP-Seq) and electrophoretic mobility shift assays to show that the Smad signal transducers directly associate with conserved Smad binding elements in regulatory regions of col-141 and col-142, but not of col-41. Hence, cuticle collagen genes are directly and indirectly regulated via the DBL-1/BMP pathway. These results provide the first direct regulatory link between this conserved signaling pathway and the collagen genes that act as its downstream effectors in body size regulation. Since collagen mutations and misregulation are implicated in numerous human genetic disorders and injury sequelae, understanding how collagen gene expression is regulated has broad implications.Author SummaryBody size in humans and other animals is determined by the combined influence of genetic and environmental factors. Failure to regulate growth and body size appropriately can lead to a variety of functional impairments and reduced fitness. Progress has been made in identifying genetic determinants of body size, but these have not often been connected into functional pathways. In the nematode model Caenorhabditis elegans, single gene mutations in the BMP signaling pathway have profound effects on body size. Here we have elucidated the BMP transcriptional network and identified cuticle collagen genes as downstream effectors of body size regulation through the BMP pathway. Collagens play diverse roles in biology; mutations are often associated with rare heritable diseases such as osteogenesis imperfecta and Ehlers-Danlos syndrome. Our work thus connects a conserved signaling pathway with its critical downstream effectors, advancing insight into how body size is specified.


2019 ◽  
Author(s):  
Matteo Ferrari ◽  
Chetan C. Rawal ◽  
Samuele Lodovichi ◽  
Achille Pellicioli

AbstractA DNA double strand break (DSB) is primed for homologous recombination (HR) repair through the nucleolytic processing (resection) of its ends, leading to the formation of a 3′ single-stranded DNA (ssDNA). Generation of the ssDNA is accompanied by the loading of several repair factors, including the ssDNA binding factor RPA and the recombinase Rad51. Then, depending upon the availability and location of a homologous sequence, different types of HR mechanisms can occur. Inefficient or slow HR repair results in the activation of the DNA damage checkpoint (DDC)1. In budding yeast, the 53BP1 ortholog Rad9 acts as a scaffold, mediating signal from upstream kinases Mec1 and Tel1 (ATR and ATM in human) to downstream effectors kinases Rad53 and Chk1 (CHK2 and CHK1 in human). In addition to its role in DDC, Rad9 limits DSB resection 2. Remarkably, this function is conserved in 53BP1, also being implicated in cancer biology in human cells 3,4.Here we show that Rad9 limits the recruitment of the helicases Sgs1 and Mph1 on to a DSB, promoting Rad51-dependent recombination with long track DNA conversions, crossovers and break-induced replication (BIR). This regulation couples the DDC with the choice and effectiveness of HR sub-pathways, and might be critical to limit genome instability with implication for cancer research.


2020 ◽  
Vol 1 (4) ◽  
pp. 252-261
Author(s):  
Tri Ardayani ◽  
Neti Sitorus

Abstrak: Setiap anak pasti mengalami pertumbuhan dan perkembangan secara alami, baik secara fisik, mental dan kematangan organ reproduksi mulai berfungsi dan karakteristik seks sekunder mulai muncul pada remaja tersebut. Usia pubertas pada anak remaja sekitar usia 10 tahun sampai 20 tahun. Pada anak perempuan masa ini ditandai dengan menstruasi (menarche), pertumbuhan payudara, tumbuhnya rambut di daerah kemaluan, sedangkan pada anak laki-laki pada masa pubertas ditandai dengan perubahan suara yang disertai dengan tonjolan kerongkongan (Adam’s apple), perubahan panjang penis, dan tumbuhnya rambut kemaluan. Pada awal memasuki masa pubertas, seorang remaja biasanya membutuhkan banyak informasi mengenai perkembangan, pertumbuhan dan perubahan yang dialaminya sehingga anak mencari informasi dengan bertanya kepada orang tua, teman, atau orang-orang yang berada di sekitar lingkunganya, tidak semua orang sekitar lingkungan remaja bisa membantu permasalahan yang dihadapi remaja sehingga mereka mencari dengan cara sendiri, misalnya dengan bertanya pada orang dewasa lainnya, dari majalah, atau bahkan dari internet. Tujuan kegiatan pengabdian masyarakat yang di lakukan oleh Sekolah Tinggi Ilmu Immanuel bekerjasama dengan SD Sukawening adalah untuk meningkatkan pengetahuan anak remaja tentang pubertas, dan mempersiapkan lebih dini datangnya masa pubertas sehingga diharapkan anak lebih siap menghadapi perubahan secara fisik dan psikologis yang akan terjadi nanti sehingga dampak negatif pubertas tidak terjadi pada anak remaja. Metode kegiatan pelaksanaan tersebut meliputi memberikan pendidikan kesehatan tentang pubertas pada anak remaja kelas 4.5.6 dan pemutaran video. Hasil kegiatan pengabdian masyarakat antara lain, pengetahuan anak meningkat tentang pubertas, anak sudah memahami perubahan yang akan terjadi pada masa pubertas baik secara fisiologis maupun secara psikologis, anak mengetahui bagaimana cara menghadapi masa pubertas dan kemana mencari informasi yang benar tentang pubertas jika mengalami masalah atau ada hal yang ingin di tanyakan tentang perubahan yang dialaminya. Peserta yang mengikuti kegiatan sebanyak 60 orang. Abstract: Adolescence experiences growth and development naturally, physically, mentally and the reproductive organs begin to function and secondary sex characteristics appeared. The age of puberty in adolescents is around the age of 10 to 20 years. The female period is being marked by menstruation (menarche), breast and pubic hair growth, while in male, puberty is characterized by voice changes accompanied by Adam's apple protrusion, changes in penis length, and pubic hair. At the beginning of puberty, adolescence usually needs a lot of information about the development, growth, and changes, thus they seek information by asking parents, friends, or people around. Sometimes, people around them will not be able to help; consequently, they search by themselves, such as asking other adults, read magazines, or even from the internet. The purpose of community service activities carried out by Immanuel School of Health Science in collaboration with SD Sukawening were to increase adolescent knowledge about puberty, and prepare for the early arrival of puberty; thus, they are expected to be better prepared facing physical and psychological changes; so that the negative impact puberty does not occur in them. The method of implementation involved providing health education about puberty and video screening to school-aged students in grades 4, 5, 6. The results of community service activities to adolescents such as increasing knowledge about puberty; understanding changes physiologically and psychologically; how to deal with puberty, and where to find correct information if they experience problems or to fulfill curiosity regarding puberty problems. There are sixty respondents participated during the program.


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