| Autor: |
Liu X; Department of Medicine (Hematology-Oncology), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Jones WD; Cell and Molecular Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Quesnel-Vallières M; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Devadiga SA; Faculty of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA., Lorent K; Department of Medicine (Gastroenterology), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Valvezan AJ; Department of Medicine (Hematology-Oncology), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Myers RL; Department of Medicine (Hematology-Oncology), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Li N; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Lengner CJ; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.; Department of Cell and Developmental Biology, Perelman School of Medicine, Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Barash Y; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Pack M; Department of Medicine (Gastroenterology), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Klein PS; Department of Medicine (Hematology-Oncology), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.; Cell and Molecular Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.; Department of Cell and Developmental Biology, Perelman School of Medicine, Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. |
| Abstrakt: |
Neural crest (NC) is a unique vertebrate cell type arising from the border of the neural plate and epidermis that gives rise to diverse tissues along the entire body axis. Roberto Mayor and colleagues have made major contributions to our understanding of NC induction, delamination, and migration. We report that a truncating mutation of the classical tumor suppressor Adenomatous Polyposis Coli ( apc) disrupts craniofacial development in zebrafish larvae, with a marked reduction in the cranial neural crest (CNC) cells that contribute to mandibular and hyoid pharyngeal arches. While the mechanism is not yet clear, the altered expression of signaling molecules that guide CNC migration could underlie this phenotype. For example, apc mcr/mcr larvae express substantially higher levels of complement c3 , which Mayor and colleagues showed impairs CNC cell migration when overexpressed. However, we also observe reduction in stroma-derived factor 1 ( sdf1/cxcl12 ), which is required for CNC migration into the head. Consistent with our previous work showing that APC directly enhances the activity of glycogen synthase kinase 3 (GSK-3) and, independently, that GSK-3 phosphorylates multiple core mRNA splicing factors, we identify 340 mRNA splicing variations in apc mutant zebrafish, including a splice variant that deletes a conserved domain in semaphorin 3f ( sema3f ), an axonal guidance molecule and a known regulator of CNC migration. Here, we discuss potential roles for apc in CNC development in the context of some of the seminal findings of Mayor and colleagues. |
