scholarly journals The BMP ligand Pinhead together with Admp supports the robustness of embryonic patterning

2019 ◽  
Vol 5 (12) ◽  
pp. eaau6455
Author(s):  
Yifang Yan ◽  
Guozhu Ning ◽  
Linwei Li ◽  
Jie Liu ◽  
Shuyan Yang ◽  
...  

Vertebrate embryonic dorsoventral axis is robustly stable in the face of variations in bone morphogenetic protein (BMP) signaling. However, the molecular mechanism behind this robustness remains uncharacterized. In this study, we show that zebrafish Pinhead, together with Admp, plays an important compensatory role in ensuring the robustness of axial patterning through fine-tuning of BMP signaling. pinhead encodes a BMP-like ligand expressed in the ventrolateral margin of the early gastrula. Transcription of pinhead and admp is under opposing regulation, where pinhead depletion results in a compensatory increase in admp transcription and vice versa, leading to normal axis formation in pinhead or admp mutants. Expression of pinhead and admp is directly repressed by the BMP/Smad pathway. When BMP signals were inhibited or excessively activated, pinhead/admp expression changed accordingly, allowing for self-regulation. Thus, this study reveals a negative feedback loop between BMP signaling and pinhead/admp that effectively stabilizes embryonic patterning by buffering against fluctuations in BMP signaling.

Development ◽  
2001 ◽  
Vol 128 (18) ◽  
pp. 3459-3472 ◽  
Author(s):  
Nipam H. Patel ◽  
David C. Hayward ◽  
Sabbi Lall ◽  
Nicole R. Pirkl ◽  
Daniel DiPietro ◽  
...  

While the expression patterns of segment polarity genes such as engrailed have been shown to be similar in Drosophila melanogaster and Schistocerca americana (grasshopper), the expression patterns of pair-rule genes such as even-skipped are not conserved between these species. This might suggest that the factors upstream of pair-rule gene expression are not conserved across insect species. We find that, despite this, many aspects of the expression of the Drosophila gap gene hunchback are shared with its orthologs in the grasshoppers S. americana and L. migratoria. We have analyzed both mRNA and protein expression during development, and find that the grasshopper hunchback orthologs appear to have a conserved role in early axial patterning of the germ anlagen and in the specification of gnathal and thoracic primordia. In addition, distinct stepped expression levels of hunchback in the gnathal/thoracic domains suggest that grasshopper hunchback may act in a concentration-dependent fashion (as in Drosophila), although morphogenetic activity is not set up by diffusion to form a smooth gradient. Axial patterning functions appear to be performed entirely by zygotic hunchback, a fundamental difference from Drosophila in which maternal and zygotic hunchback play redundant roles. In grasshoppers, maternal hunchback activity is provided uniformly to the embryo as protein and, we suggest, serves a distinct role in distinguishing embryonic from extra-embryonic cells along the anteroposterior axis from the outset of development – a distinction made in Drosophila along the dorsoventral axis later in development. Later hunchback expression in the abdominal segments is conserved, as are patterns in the nervous system, and in both Drosophila and grasshopper, hunchback is expressed in a subset of extra-embryonic cells. Thus, while the expected domains of hunchback expression are conserved in Schistocerca, we have found surprising and fundamental differences in axial patterning, and have identified a previously unreported domain of expression in Drosophila that suggests conservation of a function in extra-embryonic patterning.


Development ◽  
1996 ◽  
Vol 122 (8) ◽  
pp. 2359-2366 ◽  
Author(s):  
G.H. Thomsen

Dorsal-ventral patterning in vertebrate embryos is regulated by members of the TGF-beta family of growth and differentiation factors. In Xenopus the activins and Vg1 are potent dorsal mesoderm inducers while members of the bone morphogenetic protein (BMP) subclass pattern ventral mesoderm and regulate ectodermal cell fates. Receptors for ligands in the TGF-beta superfamily are serine-threonine kinases, but little is known about the components of the signal transduction pathway leading away from these receptors. In Drosophila the decapentaplegic protein (dpp), a homolog of vertebrate BMP-2 and BMP-4, functions in dorsal-ventral axial patterning, and a genetic screen for components involved in signaling by dpp has identified a gene named mothers against decapentaplegic (Mad). Mad encodes a unique, predicted cytoplasmic, protein containing no readily identified functional motifs. This report demonstrates that a gene closely related to Drosophila Mad exists in Xenopus (called XMad) and it exhibits activities consistent with a role in BMP signaling. XMad protein induces ventral mesoderm when overexpressed in isolated animal caps and it ventralizes embryos. Furthermore, XMad rescues phenotypes generated by a signaling-defective, dominant-negative, BMP-2/4 receptor. These results furnish evidence that XMad protein participates in vertebrate embryonic dorsal-ventral patterning by functioning in BMP-2/4 receptor signal transduction.


RSBO ◽  
2016 ◽  
Vol 12 (1) ◽  
pp. 88
Author(s):  
Lídia Audrey Rocha Valadas Marques ◽  
Edvan Alves da Costa Júnior ◽  
Mara Assef Leitão Lotif ◽  
Edilson Martins Rodrigues Neto ◽  
Francisco Filipe Carvalho da Silva ◽  
...  

Introduction: The global increase life expectancy and the resulting tooth loss has required searching for new rehabilitation alternatives in Dentistry. Biomaterials can be defined as any material that acts replacing a lost bone defect and its function. In Dentistry, many studies have aimed to improve bone regeneration through the use of BMPs for bone replacement. Objective: To review the literature on the use and clinical viability of human morphogenetic protein for the jaws reconstruction. Material and methods: The following databases were searched: Pubmed, Bireme, Lilacs, and Scielo and 30 articles published between 1965 and 2013 were found using the following descriptors: “dental implants”, “maxillary sinus”, and “biocompatible materials”. Results: Several studies demonstrate the biological advantages of rhBMP-2 on bone regeneration of the jaws. In recent years, morphogenetic protein has presented a large clinical use. Conclusion: Despite being a high-cost biomaterial, rhBMP-2 is a viable and very effective alternative for reconstruction of defects of the face.


2017 ◽  
Vol 1 ◽  
pp. 247054701771191 ◽  
Author(s):  
Eric L. Garland ◽  
Adam W. Hanley ◽  
Anne K. Baker ◽  
Matthew O. Howard

Mindfulness-based interventions have been heralded as promising means of alleviating chronic stress. While meta-analyses indicate that mindfulness-based interventions significantly reduce global measures of stress, how mindfulness-based interventions modulate the specific mechanisms underpinning chronic stress as operationalized by the National Institute of Mental Health research domain criteria (RDoC) of sustained threat has not yet been detailed in the literature. To address this knowledge gap, this article aims to (1) review evidence that mindfulness-based interventions ameliorate each of the 10 elements of behavioral dysregulation characterizing sustained threat via an array of mindful counter-regulatory strategies; (2) review evidence that mindfulness-based interventions modify biological domains implicated in sustained threat, such as the hypothalamic–pituitary–adrenal axis, as well as brain circuits involved in attentional function, limbic reactivity, habit behavior, and the default mode network; and (3) integrate these findings into a novel conceptual framework of mindful self-regulation in the face of stress—the Mindfulness-to-Meaning Theory. Taken together, the extant body of scientific evidence suggests that the practice of mindfulness enhances a range biobehavioral factors implicated in adaptive stress coping and induces self-referential plasticity, leading to the ability to find meaning in adversity. These mechanistic findings can inform the treatment development process to optimize the next generation of mindfulness-based interventions for greater therapeutic efficacy.


2021 ◽  
Vol 7 (7) ◽  
pp. eabf1798
Author(s):  
A. Murashima-Suginami ◽  
H. Kiso ◽  
Y. Tokita ◽  
E. Mihara ◽  
Y. Nambu ◽  
...  

Uterine sensitization–associated gene-1 (USAG-1) deficiency leads to enhanced bone morphogenetic protein (BMP) signaling, leading to supernumerary teeth formation. Furthermore, antibodies interfering with binding of USAG-1 to BMP, but not lipoprotein receptor–related protein 5/6 (LRP5/6), accelerate tooth development. Since USAG-1 inhibits Wnt and BMP signals, the essential factors for tooth development, via direct binding to BMP and Wnt coreceptor LRP5/6, we hypothesized that USAG-1 plays key regulatory roles in suppressing tooth development. However, the involvement of USAG-1 in various types of congenital tooth agenesis remains unknown. Here, we show that blocking USAG-1 function through USAG-1 knockout or anti–USAG-1 antibody administration relieves congenital tooth agenesis caused by various genetic abnormalities in mice. Our results demonstrate that USAG-1 controls the number of teeth by inhibiting development of potential tooth germs in wild-type or mutant mice missing teeth. Anti–USAG-1 antibody administration is, therefore, a promising approach for tooth regeneration therapy.


2020 ◽  
Vol 117 (9) ◽  
pp. 4910-4920 ◽  
Author(s):  
Joonho Suh ◽  
Na-Kyung Kim ◽  
Seung-Hoon Lee ◽  
Je-Hyun Eom ◽  
Youngkyun Lee ◽  
...  

Growth and differentiation factor 11 (GDF11) and myostatin (MSTN) are closely related transforming growth factor β (TGF-β) family members, but their biological functions are quite distinct. While MSTN has been widely shown to inhibit muscle growth, GDF11 regulates skeletal patterning and organ development during embryogenesis. Postnatal functions of GDF11, however, remain less clear and controversial. Due to the perinatal lethality ofGdf11null mice, previous studies used recombinant GDF11 protein to prove its postnatal function. However, recombinant GDF11 and MSTN proteins share nearly identical biochemical properties, and most GDF11-binding molecules have also been shown to bind MSTN, generating the possibility that the effects mediated by recombinant GDF11 protein actually reproduce the endogenous functions of MSTN. To clarify the endogenous functions of GDF11, here, we focus on genetic studies and show thatGdf11null mice, despite significantly down-regulatingMstnexpression, exhibit reduced bone mass through impaired osteoblast (OB) and chondrocyte (CH) maturations and increased osteoclastogenesis, while the opposite is observed inMstnnull mice that display enhanced bone mass. Mechanistically,Mstndeletion up-regulatesGdf11expression, which activates bone morphogenetic protein (BMP) signaling pathway to enhance osteogenesis. Also, mice overexpressing follistatin (FST), a MSTN/GDF11 inhibitor, exhibit increased muscle mass accompanied by bone fractures, unlikeMstnnull mice that display increased muscle mass without fractures, indicating that inhibition of GDF11 impairs bone strength. Together, our findings suggest that GDF11 promotes osteogenesis in contrast to MSTN, and these opposing roles of GDF11 and MSTN must be considered to avoid the detrimental effect of GDF11 inhibition when developing MSTN/GDF11 inhibitors for therapeutic purposes.


2018 ◽  
Vol 11 (5) ◽  
pp. 135
Author(s):  
Carmen Echazarreta Soler ◽  
Albert Costa Marcé

Economic crises have mainly affected the more vulnerable social sectors and created losses of freedom and inequality. Currently, most media are controlled by a relatively small group of companies around the world. In the face of this situation, networked society has accelerated the development of alternative communication models, which act as loudspeakers for citizens’ voices. The aim of this study is to describe the main features of the new forms of citizen expression, communication and cooperation, such as social networks, review sites, citizen journalism and the collaborative economy. It is concluded that in the face of these new challenges it is essential to continue to develop ethical principles of self-regulation to ensure the accuracy and thoroughness of new forms of communication on the Net.


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