Foxd3 regulates neural crest multipotency and self-renewal

Abstract

Concurrent session 4: Neural and tissue specific stem cells Program/Abstract # 29 Foxd3 regulates neural crest multipotency and self-renewal Nathan A. Mundell, Audrey Y. Frist, Patricia A. Labosky Departments of Pharmacology, Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA Center for Stem Cell Biology, Vanderbilt University, Nashville, TN, USA The neural crest (NC) is a specialized group of progenitor cells that arise from the developing spinal cord. At the onset of migration, NC is a heterogeneous pool of multipotent and fate-restricted progenitors that follow regionally defined pathways to sites of differentiation, giving rise to a variety of cell types including neurons, glia, melanocytes, smooth muscle, and cartilage. The forkhead transcription factor Foxd3 is required for self-renewal and maintenance of a multipotent state in two other progenitor cell types: embryonic stem cells and trophoblast stem cells. Foxd3 is also one of the earliest molecular markers of the NC. NC deletion of Foxd3 in the mouse embryo results in severe defects including craniofacial defects, and complete loss of the enteric nervous system. The progenitor pool is depleted and much of the NC is lost by apoptosis in mutant embryos. Lineage labeling of Foxd3 mutant embryos demonstrates that vagal NC fails to migrate into the foregut, and is greatly reduced in the outflow tract of the heart. Surprisingly, reduced cardiac NC mediates cardiovascular remodeling but not parasympathetic innervation of the heart. In vitro clonal analysis of multipotency demonstrates that Foxd3 mutant NC has reduced potency to differentiate into multiple lineages. Serial neurosphere culture experiments indicate that mutant NC does not maintain progenitor self-renewal. These results demonstrate a global role for Foxd3 in NC maintenance along the anteriorposterior axis, and establish the requirement of Foxd3 in maintenance of NC stem cell subpopulations. doi:10.1016/j.ydbio.2009.05.038 Program/Abstract # 30 The role of Gli3 in the neurogenesis of the forebrain Hui Wang, Guannan Ge, Sohyun Ahn Unit on Developmental Neurogenetics, PGD, NICHD, NIH,