Sox10 regulates enteric neural crest cell migration in the developing gut

Concurrent Sessions 1: 1.3 - Organs to organisms: Models of Human Diseases: abstract no. 1417th ISDB 2013 cum 72nd Annual Meeting of the Society for Developmental Biology, VII Latin American Society of Developmental Biology Meeting and XI Congreso de la Sociedad Mexicana de Biologia del Desarrollo. The Conference's web site is located at http://www.inb.unam.mx/isdb/Sox10 is a HMG-domain containing transcription factor which plays important roles in neural crest cell survival and differentiation. Mutations of Sox10 have been identified in patients with Waardenburg-Hirschsprung syndrome, who suffer from deafness, pigmentation defects and intestinal aganglionosis. Enteric neural crest cells (ENCCs) with Sox10 mutation undergo premature differentiation and fail to colonize the distal hindgut. It is unclear, however, whether Sox10 plays a role in the migration of ENCCs. To visualize the migration behaviour of mutant ENCCs, we generated a Sox10NGFP mouse model where EGFP is fused to the N-terminal domain of Sox10. Using time-lapse imaging, we found that ENCCs in Sox10NGFP/+ mutants displays lower migration speed and altered trajectories compared to normal controls. This behaviour was cell-autonomous, as shown by organotypic grafting of Sox10NGFP/+ gut segments onto control guts and vice versa. ENCCs encounter different extracellular matrix (ECM) molecules along the developing gut. We performed gut explant culture on various ECM and found that Sox10NGFP/+ ENCCs tend to form aggregates, particularly on fibronectin. Time-lapse imaging of single cells in gut explant culture indicated that the tightly-packed Sox10 mutant cells failed to exhibit contact inhibition of locomotion. We determined the expression of adhesion molecule families by qPCR analysis, and found integrin expression unaffected while L1-cam and selected cadherins were altered, suggesting that Sox10 mutation affects cell adhesion properties of ENCCs. Our findings identify a de novo role of Sox10 in regulating the migration behaviour of ENCCs, which has important implications for the treatment of Hirschsprung disease.postprin

The role of Sox10 in enteric neural crest cell migration

Poster presentation - Theme 3: Development & stem cellsSox10 is a transcription factor essential for maintaining the multipotency of enteric neural crest cells (ENCCs). Sox10 mutant ENCCs fail to colonize the entire gut due to premature differentiation and migration defects. By time-lapse live-cell imaging analysis, we observed that …postprin

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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The role of SOX10 in enteric neural crest cell migration

Poster Presentations: Theme 3 - Reproduction & Development, Cell Biology, and Musculoskeletal System: abstract no. 3.1

Defective cell adhesion and cell migration in Sox10 mutant neural crest

Poster Presentation: no. P43The enteric neural crest cells (ENCCs) are derived from migratory vagal neural crest cells (NCCs). Transcription factor Sox10 is crucial for ENCC multipotency maintenance. Sox10 mutant ENCCs fail to colonize the entire gut due to premature differentiation and migration defects. A Sox10NGFP mouse where EGFP is fused to the N-terminal domain of Sox10 was generated to visualize the migration behavior of mutant ENCCs. Sox10NGFP/+ mutant ENCCs form aggregates on different extracellular matrices in gut explant culture. We hypothesized that cell adhesion properties were affected in Sox10 mutant neural crest. To gain insight into the cell adhesion and molecular pathways underlying cell migration processes in ENCCs, we performed transcriptome and gene expression analysis as well as immunofluorescence analysis to study cellular phenotypes. E9.5 pre-ENCCs and E12.5 ENCCs from Wnt1-Cre:Z/EG and Sox10NGFP mutant were sorted out and performed RNA sequencing. Bioinformatics analysis indicated that among the differentially expressed genes, the expression of biological adhesion and locomotion genes were significantly affected during ENCC development. Selected differentially expressed genes were further verified by qRT-PCR. The immunostaining results of cultured explants showed that the distribution of cadherins, vinculin and FAK were affected in Sox10 mutant NCCs and ENCCs. Further cellular behavior such as real-time actin filament dynamics and intensity will be assessed by live cell imaging using Wnt1-Cre:Z/EG:Lifeact-mRFP and Sox10NGFP:Lifeact-mRFP mice, which had the ENCCs labelled by EGFP and F-actin . Our results suggest that Sox10 mutation alters the expression of cell adhesion molecules and ECM reporters, thereby may affect ENCCs cellular behavior and migration

Define the functional role of Myosin-1e at the macrophage podosome

Poster Presentation - Session 6: no. P6.1

Sox10 NGFP mutation affects migration of enteric neural cress cells in mouse embryonic gut

Conference Theme: Cells, Signals and Gene