scholarly journals Pthlha and mechanical force control early patterning of growth zones in the zebrafish craniofacial skeleton

Development ◽  
2021 ◽  
Author(s):  
Diego J. Hoyle ◽  
Daniel B. Dranow ◽  
Thomas F. Schilling

Secreted signals in patterning systems often induce repressive signals that shape their distributions in space and time. In developing growth plates (GPs) of endochondral long bones, Parathyroid hormone-like hormone (Pthlh) inhibits Indian hedgehog (Ihh) to form a negative feedback loop that controls GP progression and bone size. Whether similar systems operate in other bones and how they arise during embryogenesis remain unclear. We show that Pthlha expression in the zebrafish craniofacial skeleton precedes chondrocyte differentiation and restricts where cells undergo hypertrophy, thereby initiating a future GP. Loss of Pthlha leads to an expansion of cells expressing a novel early marker of the hypertrophic zone (HZ), entpd5a, and later HZ markers such as ihha, while local Pthlha misexpression induces ectopic entpd5a expression. Formation of this early pre-HZ correlates with onset of muscle contraction and requires mechanical force; paralysis leads to loss of entpd5a and ihha expression in the pre-HZ, mislocalized pthlha expression, and no subsequent ossification. These results suggest that local Pthlh sources combined with force determine HZ locations, establishing the negative feedback loop that later maintains GPs.

2021 ◽  
Vol 22 (16) ◽  
pp. 8472
Author(s):  
Senem Aykul ◽  
Jordan Maust ◽  
Vijayalakshmi Thamilselvan ◽  
Monique Floer ◽  
Erik Martinez-Hackert

Adipose tissues (AT) expand in response to energy surplus through adipocyte hypertrophy and hyperplasia. The latter, also known as adipogenesis, is a process by which multipotent precursors differentiate to form mature adipocytes. This process is directed by developmental cues that include members of the TGF-β family. Our goal here was to elucidate, using the 3T3-L1 adipogenesis model, how TGF-β family growth factors and inhibitors regulate adipocyte development. We show that ligands of the Activin and TGF-β families, several ligand traps, and the SMAD1/5/8 signaling inhibitor LDN-193189 profoundly suppressed 3T3-L1 adipogenesis. Strikingly, anti-adipogenic traps and ligands engaged the same mechanism of action involving the simultaneous activation of SMAD2/3 and inhibition of SMAD1/5/8 signaling. This effect was rescued by the SMAD2/3 signaling inhibitor SB-431542. By contrast, although LDN-193189 also suppressed SMAD1/5/8 signaling and adipogenesis, its effect could not be rescued by SB-431542. Collectively, these findings reveal the fundamental role of SMAD1/5/8 for 3T3-L1 adipogenesis, and potentially identify a negative feedback loop that links SMAD2/3 activation with SMAD1/5/8 inhibition in adipogenic precursors.


2016 ◽  
Vol 24 (3) ◽  
pp. 421-432 ◽  
Author(s):  
Yanbo Wang ◽  
Hongwei Liang ◽  
Geyu Zhou ◽  
Xiuting Hu ◽  
Zhengya Liu ◽  
...  

2017 ◽  
Vol 27 (15) ◽  
pp. 2260-2270.e5 ◽  
Author(s):  
Junior J. West ◽  
Teresa Zulueta-Coarasa ◽  
Janna A. Maier ◽  
Donghoon M. Lee ◽  
Ashley E.E. Bruce ◽  
...  

2020 ◽  
Vol 39 (9) ◽  
pp. 761-787
Author(s):  
Marta M. Maslej ◽  
Benoit H. Mulsant ◽  
Paul W. Andrews

Introduction: Researchers have proposed several theories of depressive rumination. To compare among them, we conducted a joint factor analysis. Methods: An online sample (n = 498) completed four rumination questionnaires and the Beck Depression Inventory. We examined associations between emerging factors and depressive symptoms. Results: Most commonly, people ruminated about solving problems in their lives, followed by the causes or consequences of negative situations. They least commonly ruminated about their symptoms and sadness. Thoughts about symptoms and causes or consequences of negative situations uniquely related to depressive symptoms. There was a circular covariance relation between depressive symptoms, thoughts about causes or consequences, and problem-solving, suggesting that symptoms are regulated by a negative feedback loop involving problem-solving. This feedback was not present unless models included thoughts about causes or consequences, suggesting that these thoughts benefit problem-solving. Discussion: Depressive rumination may be a dynamic process involving various thoughts, with different combinations of thoughts having different consequences for depression.


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