Role of BMP signaling during early development of the annelid Capitella teleta

AbstractThe mechanisms regulating nervous system development are still unknown for a wide variety of taxa. In insects and vertebrates, bone morphogenetic protein (BMP) signaling is known to play a key role in both neural specification and dorsal-ventral (D-V) axis formation, leading to speculation about the conserved evolution of nervous systems. Studies outside insects and vertebrates show a more diverse picture of what, if any role, BMP signaling plays in neural development across Bilateria. This is especially true in the morphologically diverse Spiralia (~Lophotrochozoa). Despite several studies of D-V axis formation and neural induction in spiralians, there is no consensus for how these two processes are related, or whether BMP signaling may have played an ancestral role in either process. Here we incubated larvae of the sedentary annelid Capitella teleta in BMP4 protein at various cleavage stages to determine the role of BMP signaling during early development. Adding exogenous BMP protein to early-cleaving C. teleta embryos had a striking effect on formation of the brain, eyes, and foregut in a time-dependent manner. However, adding BMP did not block neural specification of the brain or VNC or block formation of the D-V axis. We identified three key time windows of BMP activity, and hypothesize that BMP may cause trans-fate switching of blastomere quadrant identities in at least one time window. 1. Early treatment around 2q caused the loss of the eyes, radialization of the brain, and a reduction of the foregut, which we interpret as a loss of A-, B- and C-quadrant identities with a possible trans-fate switch to a D-quadrant identity. 2. Treatment after 4q induced formation of a third ectopic brain lobe, eye, and foregut lobe, which we interpret as a trans-fate switch of B-quadrant micromeres to a C-quadrant identity. 3. Continuous BMP treatment from early cleavage through mid-larval stages resulted in a modest expansion of Ct-chrdl expression in the dorsal ectoderm and a concomitant loss of the ventral midline (neurotroch ciliary band). Loss of the ventral midline was accompanied by a collapse of the bilaterally-symmetric VNC although the total amount of neural tissue did not appear to be greatly affected. Our results compared to those from other annelids and molluscs suggest that BMP signaling was not ancestrally involved in delimiting neural tissue or establishing the D-V axis in the last common ancestor of annelids. However, the effects of ectopic BMP on quadrant-identity during cleavage stages may represent a very early ‘organizing’ function in the context of spiralian development. Ultimately, studies on a wider range of spiralian taxa are needed to determine if the ability of BMP signaling to block neural induction and help establish the D-V axis was lost within Annelida or if BMP signaling gained these functions multiple times across Bilateria. Ultimately, these comparisons will give us insight into the evolutionary origins of centralized nervous systems and body plans.

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Early Development of the Romania's Banking System and the Role of Foreign Banks

SSRN Electronic Journal ◽

10.2139/ssrn.1300311 ◽

2008 ◽

Author(s):

Arnaldo Mauri ◽

Claudia Gabriela Baicu

Keyword(s):

Early Development ◽

Banking System ◽

Foreign Banks

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The Role of BMP Signaling in Osteoclast Regulation

Journal of Developmental Biology ◽

10.3390/jdb9030024 ◽

2021 ◽

Vol 9 (3) ◽

pp. 24

Author(s):

Brian Heubel ◽

Anja Nohe

Keyword(s):

Bone Formation ◽

Bone Morphogenetic Proteins ◽

Bone Diseases ◽

Bmp Signaling ◽

Bone Homeostasis ◽

Direct Stimulation ◽

Federal Drug Administration ◽

Bmp Pathway ◽

Stimulation Of

The osteogenic effects of Bone Morphogenetic Proteins (BMPs) were delineated in 1965 when Urist et al. showed that BMPs could induce ectopic bone formation. In subsequent decades, the effects of BMPs on bone formation and maintenance were established. BMPs induce proliferation in osteoprogenitor cells and increase mineralization activity in osteoblasts. The role of BMPs in bone homeostasis and repair led to the approval of BMP2 by the Federal Drug Administration (FDA) for anterior lumbar interbody fusion (ALIF) to increase the bone formation in the treated area. However, the use of BMP2 for treatment of degenerative bone diseases such as osteoporosis is still uncertain as patients treated with BMP2 results in the stimulation of not only osteoblast mineralization, but also osteoclast absorption, leading to early bone graft subsidence. The increase in absorption activity is the result of direct stimulation of osteoclasts by BMP2 working synergistically with the RANK signaling pathway. The dual effect of BMPs on bone resorption and mineralization highlights the essential role of BMP-signaling in bone homeostasis, making it a putative therapeutic target for diseases like osteoporosis. Before the BMP pathway can be utilized in the treatment of osteoporosis a better understanding of how BMP-signaling regulates osteoclasts must be established.

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The Role of Serotonin in the Development of Psychiatric Disorders: Studies on Drug Dependence and Anxiety-like Behaviour Following the Genetic Reduction of the Serotonin Transporter

10.26686/wgtn.17013845 ◽

2021 ◽

Author(s):

◽

Alana Oakly

Keyword(s):

Psychiatric Disorders ◽

Early Development ◽

Drug Dependence ◽

Primary Objective ◽

Behavioural Response ◽

Mrna Levels ◽

Self Administration ◽

Knock Out ◽

Enhanced Sensitivity

<p>Rationale: Given the high prevalence and large burden of psychiatric disorders it is imperative to determine the underling etiology in order for better understanding and treatment. The neurotransmitter serotonin (5-HT) has been associated with mental disorders in humans both pharmacologically and genetically. Individuals with the short-allele of a prominent polymorphism within the 5-HT transporter (SERT) show increased incidence of mood disorders and drug dependence. However, whether or not dysregulation in the 5-HT system causes, or is just associated with, psychiatric disorders is impossible to determine from human studies alone. Consequently, it is imperative to employ an animal model of down-regulated SERT function. To better understand the role of 5-HT in drug dependence, the rat’s behavioural response to the psychostimulant (±) 3, 4-methylenedioxymethamphetamine (MDMA), a preferentially serotonergically mediated drug, was assessed. Finally, the ability to rescue the anxiety-like phenotype in the SERT-/- rat by altering extracellular 5-HT during early development was also evaluated. Objective: The primary objective of the current thesis was to determine whether dysregulation of 5-HT is directly linked to the occurrence of psychiatric disorders, particularly drug dependence and anxiety. Methods: A model of down-regulated SERT function, the SERT knock-out (SERT-/-) rat, was used for all experiments in order to determine a causal relationship between 5-HT dysregulation and psychiatric disorders. In Chapter 2, the response of the SERT-/- rats to various tasks usually disrupted by MDMA was assessed. In Chapter 3, the sensitivity of the SERT-/- rats to the reinforcing effects of MDMA was determined using the self-administration paradigm. Finally, in Chapter 4, whether the anxiety-like behaviour of the SERT-/- rat could be rescued through normalising excessive extracellular 5-HT neonatally was assessed. An attempt was also made to determine a mechanism by which 5-HT dysregulation could alter behaviour. To this end, gene expression previously found to be up- or down-regulated in the SERT-/- rat was assessed in the neonatally treated rats. Results: The results of Chapter 2 indicated the SERT is necessary for MDMA’s disruption of startle habituation but not its psychomotor effects. Moreover, for those rats that could discriminate low dose MDMA from saline, genetic removal of the SERT resulted in the inability to discriminate MDMA from amphetamine, implying that, in these rats, MDMA was now subjectively indistinguishable from amphetamine. Indeed, this alteration also resulted in enhanced sensitivity to the reinforcing properties of MDMA, giving MDMA the qualities of a traditional psychostimulant in SERT-/- rats (Chapter 3). Finally, lowering the excessive 5-HT during neonatal development in SERT-/- rats led to a rescue of mild, but not high, anxiety-like behaviour in males. However, mRNA levels of long 3’NTR BDNF and 5-HT1a, genes associated with neurodevelopment, remained unchanged across genotypes and treatment groups (Chapter 4). Conclusions: Genetic removal of the 5-HT transporter results in an altered behavioural response to MDMA, in particular an increased sensitivity to its reinforcing properties. However, while the genetic removal of the SERT results in enhanced extracellular 5-HT, the pathological phenotypes present in this rat are likely due to this increase occurring in early development, not its continued presence in adulthood. Overall, these findings contribute to the growing body of literature indicating that enhanced brain 5-HT during early development can lead to pathological behaviour in adulthood.</p>

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Abstract 73: Bone Morphogenetic Protein Activity Modulates Endothelial Barrier Function

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.32.suppl_1.a73 ◽

2012 ◽

Vol 32 (suppl_1) ◽

Author(s):

Thomas Helbing ◽

Elena Ketterer ◽

Bianca Engert ◽

Jennifer Heinke ◽

Sebastian Grundmann ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Barrier Function ◽

Endothelial Permeability ◽

Bmp Signaling ◽

Endothelial Barrier ◽

Endothelial Barrier Function

Introduction: Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome, are associated with high morbidity and mortality in patients. During the progression of ALI, the endothelial cell barrier of the pulmonary vasculature becomes compromised, leading to pulmonary edema, a characteristic feature of ALI. It is well-established that EC barrier dysfunction is initiated by cytoskeletal remodeling, which leads to disruption of cell-cell contacts and formation of paracellular gaps, allowing penetration of protein-rich fluid and inflammatory cells. Bone morphogenetic proteins (BMPs) are important players in endothelial dysfunction and inflammation but their effects on endothelial permeability in ALI have not been investigated until now. Methods and Results: As a first approach to assess the role of BMPs in acute lung injury we analysed BMP4 and BMPER expression in an infectious (LPS) and a non-infectious (bleomycin) mouse models of acute lung injury. In both models BMP4 and BMPER protein expression levels were reduced demonstrated by western blots, suggesting that BMPs are involved in progression ALI. To assess the role of BMPs on vascular leakage, a key feature of ALI, BMP activity in mice was inhibited by i.p. administration of LDN193189, a small molecule that blocks BMP signalling. After 3 days Evans blue dye (EVB) was administered i.v. and dye extravasation into the lungs was quantified as a marker for vascular leakage. Interestingly, LDN193189 significantly increased endothelial permeability compared to control lungs, indicating that BMP signaling is involved in maintenance of endothelial barrier function. To quantify effects of BMP inhibition on endothelial barrier function in vitro, HUVECs were seeded onto transwell filters and were exposed to LDN193189. After 3 days FITC-dextrane was added and passage into the lower chamber was quantified as a marker for endothelial barrier function. Thrombin served as a positive control. As expected from our in vivo experiments inhibition of BMP signaling by LDN193189 enhanced FITC-dextrane passage. To study specific effects of BMPs on endothelial barrier function, two protagonist of the BMP family, BMP2 and BMP4, or BMP modulator BMPER were tested in the transwell assay in vitro. Interestingly BMP4 and BMPER, but not BMP2, reduced FITC-dextrane passage demonstrating that BMP4 and BMPER improved endothelial barrier function. Vice versa, specific knock down of BMP4 or BMPER increased leakage in transwell assays. Im immuncytochemistry silencing of BMPER or BMP4 induced hyperpermeability as a consequence of a pro-inflammatory endothelial phenotype characterised by reduced cell-cell contacts and increased actin stress fiber formation. Additionally, the pro-inflammatory endothelial phenotype was confirmed by real-time revealing increased expression of adhesion molecules ICAM-1 or proinflammatory cytokines such as IL-6 and IL-8 in endothelial cells after BMPER or BMP4 knock down. Confirming these in vitro results BMPER +/- mice exhibit increased extravasation of EVB into the lungs, indicating that partial loss of BMPER impairs endothelial barrier function in vitro and in vivo. Conclusion: We identify BMPER and BMP4 as local regulators of vascular permeability. Both are protective for endothelial barrier function and may open new therapeutic avenues in the treatment of acute lung injury.

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The zebrafish calpain system – expression and role of calpain and calpastatin during early development

Developmental Biology ◽

10.1016/j.ydbio.2007.03.481 ◽

2007 ◽

Vol 306 (1) ◽

pp. 437

Author(s):

Stephanie E. Lepage ◽

Isaac Skromne ◽

Ashley E. Bruce

Keyword(s):

Early Development ◽

Calpain System

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The interplay of genotype and environment in the development of fear and anxiety

e-Neuroforum ◽

10.1007/s13295-013-0045-1 ◽

2013 ◽

Vol 19 (3) ◽

Author(s):

N. Sachser ◽

K.-P. Lesch

Keyword(s):

Individual Differences ◽

Environmental Factors ◽

Anxiety Disorders ◽

Candidate Gene ◽

Early Development ◽

Genetic Variants ◽

External Influences ◽

Postnatal Environment ◽

Fear And Anxiety

AbstractIndividual differences in fear, anxiety, and the etiology of anxiety disorders develop during ontogeny. They are due to both genetic and environmental factors. With regard to the role of the environment, the organism is most susceptible to external influences during early development. Accordingly, stressors that impinge on the maternal organism during pregnancy evoke high levels of anxiety in the offspring later in life, as does an adverse early postnatal environment. However, anxiety-related circuits in the central nervous system retain their plasticity in adulthood, i.e., levels of anxiety can also be modified by experience across the entire successive lifespan. Notably, the effects of external stressors on the individual’s level of anxiety are modulated by genotype. Such genotype-by-environment interactions are particularly well studied in relation to genetic variants that modulate the function of the serotonin transporter. Thus, this review focuses on this candidate gene to elucidate the interplay of genotype and environment in the development of fear and anxiety.

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Role of oxygen in early development and embryonic stem cell derivation

Stem Cells in Human Reproduction ◽

10.1201/b14459-19 ◽

2006 ◽

pp. 201-210

Keyword(s):

Stem Cell ◽

Embryonic Stem Cell ◽

Early Development ◽

Embryonic Stem ◽

Stem Cell Derivation

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The Contribution of Muslims and Islamic Concepts: Rethinking and Establishing the Actual Origin of Concepts and Thought in Psychology

International Journal of Indian Psychology ◽

10.25215/0402.187 ◽

2017 ◽

Vol 4 (2) ◽

Author(s):

Ajmal Majeed ◽

Jabir K.P

Keyword(s):

Early Development ◽

Well Being ◽

Great Role ◽

Ibn Sina ◽

The Real ◽

Western Countries ◽

Development Period ◽

Academic Discussion ◽

Muslim Scholars

The paper deals with contribution of Muslim philosophers, scholars, scientists and psychologists for psychology in the early development period of psychology. One of the major aim of this paper is to re-evaluate the real and factual origin of concepts about the treatments, theories, psycho-therapies, meditation etc. Today the western countries are ruling over the psychology development. The paper explains and establishes the argument that the Concepts and theories are formed with the contribution of Muslim thoughts and ideas. Islamic approaches and interpretation play a role in the advancement of psychology. The paper focuses on several Muslim scholars like Imam Ghazali, Ashraf Ali Yhanvi, Muhammad ibn Zakariya al-Razi, Abu-Ali al-Husayn ibn Abdalah ibn-Sina,etc. whose contributions are not mentioned in any academic discussion or textbooks of psychology or related publication. So the paper will be a thoughtful work for the psychologists to rethink about the contribution and the role of Islam and Muslims in psychology. Prophet Muhammed (pbuh) is one of the best person who lived in this world to lead the humans toward well- being in all perspectives of life. The paper concludes with the argument that the Islamic concepts and Muslim scholars have a great role in the advancement of psychology.

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