scholarly journals Downregulation of microRNA‐431‐5p promotes enteric neural crest cell proliferation via targetingLRSAM1 in Hirschsprung's disease

2019 ◽  
Vol 61 (4) ◽  
pp. 294-302
Author(s):  
Bo Hu ◽  
Lei Cao ◽  
Xiao‐ye Wang ◽  
Long Li
Keyword(s):  
Cell Proliferation ◽  
Neural Crest ◽  
Hirschsprung's Disease ◽  
Hirschsprung’S Disease ◽  
Neural Crest Cell ◽  
Crest Cell

scholarly journals Hirschsprung’s disease and variants in genes that regulate enteric neural crest cell proliferation, migration and differentiation

2012 ◽  
Vol 57 (8) ◽  
pp. 485-493 ◽  
Author(s):  
Tonia C Carter ◽  
Denise M Kay ◽  
Marilyn L Browne ◽  
Aiyi Liu ◽  
Paul A Romitti ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Neural Crest ◽  
Hirschsprung's Disease ◽  
Hirschsprung’S Disease ◽  
Neural Crest Cell ◽  
Crest Cell

scholarly journals Cell proliferation drives neural crest cell invasion of the intestine

2007 ◽  
Vol 302 (2) ◽  
pp. 553-568 ◽  
Author(s):  
Matthew J. Simpson ◽  
Dong C. Zhang ◽  
Michael Mariani ◽  
Kerry A. Landman ◽  
Donald F. Newgreen
Keyword(s):  
Cell Proliferation ◽  
Neural Crest ◽  
Cell Invasion ◽  
Neural Crest Cell ◽  
Crest Cell

scholarly journals tp53-dependent and independent signaling underlies the pathogenesis and possible prevention of Acrofacial Dysostosis–Cincinnati type

2018 ◽  
Vol 27 (15) ◽  
pp. 2628-2643 ◽  
Author(s):  
Kristin E N Watt ◽  
Cynthia L Neben ◽  
Shawn Hall ◽  
Amy E Merrill ◽  
Paul A Trainor
Keyword(s):  
Cell Proliferation ◽  
Neural Crest ◽  
Ribosome Biogenesis ◽  
Neural Crest Cell ◽  
Protein Translation ◽  
Rdna Transcription ◽  
Zebrafish Model ◽  
Pathogenic Variants ◽  
Rrna Transcription ◽  
Crest Cell

Abstract Ribosome biogenesis is a global process required for growth and proliferation in all cells, but disruptions in this process surprisingly lead to tissue-specific phenotypic disorders termed ribosomopathies. Pathogenic variants in the RNA Polymerase (Pol) I subunit POLR1A cause Acrofacial Dysostosis–Cincinnati type, which is characterized by craniofacial and limb anomalies. In a zebrafish model of Acrofacial Dysostosis–Cincinnati type, we demonstrate that polr1a–/– mutants exhibit deficient 47S rRNA transcription, reduced monosomes and polysomes and, consequently, defects in protein translation. This results in Tp53-dependent neuroepithelial apoptosis, diminished neural crest cell proliferation and cranioskeletal anomalies. This indicates that POLR1A is critical for rRNA transcription, which is considered a rate limiting step in ribosome biogenesis, underpinning its requirement for neuroepithelial cell and neural crest cell proliferation and survival. To understand the contribution of the Tp53 pathway to the pathogenesis of Acrofacial Dysostosis–Cincinnati type, we genetically inhibited tp53 in polr1a–/– mutant embryos. Tp53 inhibition suppresses neuroepithelial apoptosis and partially ameliorates the polr1a mutant phenotype. However, complete rescue of cartilage development is not observed due to the failure to improve rDNA transcription and neural crest cell proliferation. Altogether, these data reveal specific functions for both Tp53-dependent and independent signaling downstream of polr1a in ribosome biogenesis during neural crest cell and craniofacial development, in the pathogenesis of Acrofacial Dysostosis–Cincinnati type. Furthermore, our work sets the stage for identifying Tp53-independent therapies to potentially prevent Acrofacial dysostosis–Cincinnati type and other similar ribosomopathies.

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