scholarly journals Myocardin-related transcription factors regulate the Cdk5/Pctaire1 kinase cascade to control neurite outgrowth, neuronal migration and brain development

Development ◽  
2010 ◽  
Vol 137 (14) ◽  
pp. 2365-2374 ◽  
Author(s):  
M. H. Mokalled ◽  
A. Johnson ◽  
Y. Kim ◽  
J. Oh ◽  
E. N. Olson
Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 611
Author(s):  
Kelly Coffey

Identifying novel therapeutic targets for the treatment of prostate cancer (PC) remains a key area of research. With the emergence of resistance to androgen receptor (AR)-targeting therapies, other signalling pathways which crosstalk with AR signalling are important. Over recent years, evidence has accumulated for targeting the Hippo signalling pathway. Discovered in Drosophila melanogasta, the Hippo pathway plays a role in the regulation of organ size, proliferation, migration and invasion. In response to a variety of stimuli, including cell–cell contact, nutrients and stress, a kinase cascade is activated, which includes STK4/3 and LATS1/2 to inhibit the effector proteins YAP and its paralogue TAZ. Transcription by their partner transcription factors is inhibited by modulation of YAP/TAZ cellular localisation and protein turnover. Trnascriptional enhanced associate domain (TEAD) transcription factors are their classical transcriptional partner but other transcription factors, including the AR, have been shown to be modulated by YAP/TAZ. In PC, this pathway can be dysregulated by a number of mechanisms, making it attractive for therapeutic intervention. This review looks at each component of the pathway with a focus on findings from the last year and discusses what knowledge can be applied to the field of PC.


Endocrinology ◽  
2013 ◽  
Vol 154 (1) ◽  
pp. 388-399 ◽  
Author(s):  
Youli Hu ◽  
Subathra Poopalasundaram ◽  
Anthony Graham ◽  
Pierre-Marc Bouloux

Fibroblast growth factor (FGF) signaling is essential for both olfactory bulb (OB) morphogenesis and the specification, migration, and maturation of the GnRH-secreting neurons. Disruption of FGF signaling contributes to Kallmann syndrome characterized by both anosmia and sexual immaturity. However, several unanswered questions remain as to which specific FGF receptor (FGFR)-1 signaling pathways are necessary for OB and GnRH neuronal development. Here, using pharmacological phosphatidylinositol 3-kinase (PI3K) isoform-specific inhibitors, we demonstrate a central role for the PI3K p110α isoform as a downstream effector of FGFR1 signaling for both GnRH neuronal migration and OB development. We show that signaling via the PI3K p110α isoform is required for GnRH neuronal migration in explant cultures of embryonic day (E) 4 chick olfactory placodes. We also show that in ovo administration of LY294002, a global PI3K inhibitor as well as an inhibitor to the PI3K p110α isoform into the olfactory placode of E3 chick embryo impairs GnRH neuronal migration toward the forebrain. In contrast, in ovo PI3K inhibitor treatment produced no obvious defects on primary olfactory sensory neuron axonal targeting and bundle formation. We also demonstrate that anosmin-1 and FGF2 induced neuronal migration of immortalized human embryonic GnRH neuroblast cells (FNC-B4-hTERT) is mediated by modulating FGFR1 signaling via the PI3K p110α isoform, specifically through phosphorylation of the PI3K downstream effectors, Akt and glycogen synthase kinase-3β. Finally, we show that neurite outgrowth and elongation of OB neurons in E10 chick OB explants are also dependent on the PI3K p110α isoform downstream of FGFR1. This study provides mechanistic insight into the etiology of Kallmann syndrome.


Cytoskeleton ◽  
2016 ◽  
Vol 73 (9) ◽  
pp. Spc1-Spc1
Author(s):  
Tiago J. Dantas ◽  
Aurelie Carabalona ◽  
Daniel Jun-Kit Hu ◽  
Richard B. Vallee

Neuroforum ◽  
2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Mira Jakovcevski ◽  
Geraldine Zimmer-Bensch

Abstract Brain development comprises a fine-tuned ensemble of molecular processes that need to be orchestrated in a very coordinated way throughout time and space. A wide array of epigenetic mechanisms, ranging from DNA methylation and histone modifications to noncoding RNAs, have been identified for their major role in guiding developmental processes such as progenitor proliferation, neuronal migration, and differentiation through precise regulation of gene expression programs. The importance of epigenetic processes during development is reflected by the high prevalence of neurodevelopmental diseases which are caused by a lack or mutation of genes encoding for transcription factors and other epigenetic regulators. Most of these factors process central functions for proper brain development, and respective mutations lead to severe cognitive defects. A better understanding of epigenetic programs during development might open new routes toward better treatment options for related diseases.


2018 ◽  
Vol 9 (10) ◽  
Author(s):  
Weizhe Liu ◽  
Fang Han ◽  
Shuai Qu ◽  
Yuanfei Yao ◽  
Jianxiang Zhao ◽  
...  

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e46592 ◽  
Author(s):  
Gum Hwa Lee ◽  
Sun Hong Kim ◽  
Ramin Homayouni ◽  
Gabriella D'Arcangelo

2015 ◽  
Vol 57 (4) ◽  
pp. 463-469 ◽  
Author(s):  
Runchuan Yan ◽  
Xinde Hu ◽  
Qi Zhang ◽  
Lingzhen Song ◽  
Mengdi Zhang ◽  
...  

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