Notch and NFκB signaling pathways: Do they collaborate in normal vertebrate brain development and function?

BioEssays ◽  
2007 ◽  
Vol 29 (10) ◽  
pp. 1039-1047 ◽  
Author(s):  
Hwee-Luan Ang ◽  
Vinay Tergaonkar
2021 ◽  
Vol 12 ◽  
Author(s):  
Austin Ferro ◽  
Yohan S. S. Auguste ◽  
Lucas Cheadle

Intercellular signaling molecules such as cytokines and their receptors enable immune cells to communicate with one another and their surrounding microenvironments. Emerging evidence suggests that the same signaling pathways that regulate inflammatory responses to injury and disease outside of the brain also play powerful roles in brain development, plasticity, and function. These observations raise the question of how the same signaling molecules can play such distinct roles in peripheral tissues compared to the central nervous system, a system previously thought to be largely protected from inflammatory signaling. Here, we review evidence that the specialized roles of immune signaling molecules such as cytokines in the brain are to a large extent shaped by neural activity, a key feature of the brain that reflects active communication between neurons at synapses. We discuss the known mechanisms through which microglia, the resident immune cells of the brain, respond to increases and decreases in activity by engaging classical inflammatory signaling cascades to assemble, remodel, and eliminate synapses across the lifespan. We integrate evidence from (1) in vivo imaging studies of microglia-neuron interactions, (2) developmental studies across multiple neural circuits, and (3) molecular studies of activity-dependent gene expression in microglia and neurons to highlight the specific roles of activity in defining immune pathway function in the brain. Given that the repurposing of signaling pathways across different tissues may be an important evolutionary strategy to overcome the limited size of the genome, understanding how cytokine function is established and maintained in the brain could lead to key insights into neurological health and disease.


Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 249
Author(s):  
Mengqi Dong ◽  
Yuanyuan Li ◽  
Min Zhu ◽  
Jinbo Li ◽  
Zhanfen Qin

Although tetrabromobisphenol A (TBBPA) has been well proven to disturb TH signaling in both in vitro and in vivo assays, it is still unclear whether TBBPA can affect brain development due to TH signaling disruption. Here, we employed the T3-induced Xenopus metamorphosis assay (TIXMA) and the spontaneous metamorphosis assay to address this issue. In the TIXMA, 5–500 nmol/L TBBPA affected T3-induced TH-response gene expression and T3-induced brain development (brain morphological changes, cell proliferation, and neurodifferentiation) at premetamorphic stages in a complicated biphasic concentration-response manner. Notably, 500 nmol/L TBBPA treatment alone exerted a stimulatory effect on tadpole growth and brain development at these stages, in parallel with a lack of TH signaling activation, suggesting the involvement of other signaling pathways. As expected, at the metamorphic climax, we observed inhibitory effects of 50–500 nmol/L TBBPA on metamorphic development and brain development, which was in agreement with the antagonistic effects of higher concentrations on T3-induced brain development at premetamorphic stages. Taken together, all results demonstrate that TBBPA can disturb TH signaling and subsequently interfere with TH-dependent brain development in Xenopus; meanwhile, other signaling pathways besides TH signaling could be involved in this process. Our study improves the understanding of the effects of TBBPA on vertebrate brain development.


Author(s):  
Rachel L. Leon ◽  
Imran N. Mir ◽  
Christina L. Herrera ◽  
Kavita Sharma ◽  
Catherine Y. Spong ◽  
...  

Abstract Children with congenital heart disease (CHD) are living longer due to effective medical and surgical management. However, the majority have neurodevelopmental delays or disorders. The role of the placenta in fetal brain development is unclear and is the focus of an emerging field known as neuroplacentology. In this review, we summarize neurodevelopmental outcomes in CHD and their brain imaging correlates both in utero and postnatally. We review differences in the structure and function of the placenta in pregnancies complicated by fetal CHD and introduce the concept of a placental inefficiency phenotype that occurs in severe forms of fetal CHD, characterized by a myriad of pathologies. We propose that in CHD placental dysfunction contributes to decreased fetal cerebral oxygen delivery resulting in poor brain growth, brain abnormalities, and impaired neurodevelopment. We conclude the review with key areas for future research in neuroplacentology in the fetal CHD population, including (1) differences in structure and function of the CHD placenta, (2) modifiable and nonmodifiable factors that impact the hemodynamic balance between placental and cerebral circulations, (3) interventions to improve placental function and protect brain development in utero, and (4) the role of genetic and epigenetic influences on the placenta–heart–brain connection. Impact Neuroplacentology seeks to understand placental connections to fetal brain development. In fetuses with CHD, brain growth abnormalities begin in utero. Placental microstructure as well as perfusion and function are abnormal in fetal CHD.


Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2693
Author(s):  
Gabriella Schiera ◽  
Carlo Maria Di Liegro ◽  
Italia Di Liegro

The development and maturation of the mammalian brain are regulated by thyroid hormones (THs). Both hypothyroidism and hyperthyroidism cause serious anomalies in the organization and function of the nervous system. Most importantly, brain development is sensitive to TH supply well before the onset of the fetal thyroid function, and thus depends on the trans-placental transfer of maternal THs during pregnancy. Although the mechanism of action of THs mainly involves direct regulation of gene expression (genomic effects), mediated by nuclear receptors (THRs), it is now clear that THs can elicit cell responses also by binding to plasma membrane sites (non-genomic effects). Genomic and non-genomic effects of THs cooperate in modeling chromatin organization and function, thus controlling proliferation, maturation, and metabolism of the nervous system. However, the complex interplay of THs with their targets has also been suggested to impact cancer proliferation as well as metastatic processes. Herein, after discussing the general mechanisms of action of THs and their physiological effects on the nervous system, we will summarize a collection of data showing that thyroid hormone levels might influence cancer proliferation and invasion.


2014 ◽  
Vol 9 (2) ◽  
pp. 154-164 ◽  
Author(s):  
Danya Glaser

Purpose – The purpose of this paper is to outline brain structure and development, the relationship between environment and brain development and implications for practice. Design/methodology/approach – The paper is based on a selected review of the literature and clinical experience. Findings – While genetics determine the sequence of brain maturation, the nature of brain development and functioning is determined by the young child's caregiving environment, to which the developing brain constantly adapts. The absence of input during sensitive periods may lead to later reduced functioning. There is an undoubted immediate equivalence between every mind function – emotion, cognition, behaviour and brain activity, although the precise location of this in the brain is only very partially determinable, since brain connections and function are extremely complex. Originality/value – This paper provides an overview of key issues in neurodevelopment relating to the development of young children, and implications for policy and practice.


Development ◽  
2001 ◽  
Vol 128 (15) ◽  
pp. 3001-3015 ◽  
Author(s):  
Pamela L. Bradley ◽  
Deborah J. Andrew

During development, directed cell migration is crucial for achieving proper shape and function of organs. One well-studied example is the embryonic development of the larval tracheal system of Drosophila, in which at least four signaling pathways coordinate cell migration to form an elaborate branched network essential for oxygen delivery throughout the larva. FGF signaling is required for guided migration of all tracheal branches, whereas the DPP, EGF receptor, and Wingless/WNT signaling pathways each mediate the formation of specific subsets of branches. Here, we characterize ribbon, which encodes a BTB/POZ-containing protein required for specific tracheal branch migration. In ribbon mutant tracheae, the dorsal trunk fails to form, and ventral branches are stunted; however, directed migrations of the dorsal and visceral branches are largely unaffected. The dorsal trunk also fails to form when FGF or Wingless/WNT signaling is lost, and we show that ribbon functions downstream of, or parallel to, these pathways to promote anterior-posterior migration. Directed cell migration of the salivary gland and dorsal epidermis are also affected in ribbon mutants, suggesting that conserved mechanisms may be employed to orient cell migrations in multiple tissues during development.


2019 ◽  
Author(s):  
Madeline Farber ◽  
Dylan Gee ◽  
Ahmad R. Hariri

Studies of early adversity such as trauma, abuse, and neglect highlight the critical importance of quality caregiving in brain development and mental health. However, the impact of normative range variability in caregiving on such biobehavioral processes remains poorly understood. Thus, we lack an essential foundation for understanding broader, population-representative developmental mechanisms of risk and resilience. Here, we conduct a scoping review of the extant literature centered on the question, “Is variability in normative range parenting associated with variability in brain structure and function?” After removing duplicates and screening by title, abstract, and full-text, 23 records were included in a qualitative review. The most striking outcome of this review was not only how few studies have explored associations between brain development and normative range parenting, but also how little methodological consistency exists across published studies. In light of these limitations, we propose recommendations for future research on normative range parenting and brain development. In doing so, we hope to facilitate evidence-based research that will help inform policies and practices that yield optimal developmental trajectories and mental health.


2018 ◽  
Author(s):  
Kathryn L. Mills ◽  
Christian K. Tamnes

The development of the human brain involves a prolonged course of maturation, enabling us to learn to navigate our complex social environments. Here, we give short introductions to post-mortem and animal studies on postnatal brain development and selected methodological considerations for longitudinal developmental neuroimaging. We then describe typical developmental changes in brain structure and function from childhood to adulthood. We focus on measurements derived from magnetic resonance imaging (MRI) and on longitudinal data. Specifically, we discuss brain structural development based on morphometry and diffusion tensor imaging (DTI) studies, and functional development based on resting-state and task-based functional MRI. Finally, we highlight selected current overarching research questions and argue that an important step in answering these questions is to study individual differences in longitudinal brain development.


Sign in / Sign up

Export Citation Format

Share Document