Browsing by Subject "Neural Crest"

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Open Access
Temperature-activated ion channels in neural crest cells confer maternal fever-associated birth defects.
(Science signaling, 2017-10) Hutson, Mary R; Keyte, Anna L; Hernández-Morales, Miriam; Gibbs, Eric; Kupchinsky, Zachary A; Argyridis, Ioannis; Erwin, Kyle N; Pegram, Kelly; Kneifel, Margaret; Rosenberg, Paul B; Matak, Pavle; Xie, Luke; Grandl, Jörg; Davis, Erica E; Katsanis, Nicholas; Liu, Chunlei; Benner, Eric J
Birth defects of the heart and face are common, and most have no known genetic cause, suggesting a role for environmental factors. Maternal fever during the first trimester is an environmental risk factor linked to these defects. Neural crest cells are precursor populations essential to the development of both at-risk tissues. We report that two heat-activated transient receptor potential (TRP) ion channels, TRPV1 and TRPV4, were present in neural crest cells during critical windows of heart and face development. TRPV1 antagonists protected against the development of hyperthermia-induced defects in chick embryos. Treatment with chemical agonists of TRPV1 or TRPV4 replicated hyperthermia-induced birth defects in chick and zebrafish embryos. To test whether transient TRPV channel permeability in neural crest cells was sufficient to induce these defects, we engineered iron-binding modifications to TRPV1 and TRPV4 that enabled remote and noninvasive activation of these channels in specific cellular locations and at specific developmental times in chick embryos with radio-frequency electromagnetic fields. Transient stimulation of radio frequency-controlled TRP channels in neural crest cells replicated fever-associated defects in developing chick embryos. Our data provide a previously undescribed mechanism for congenital defects, whereby hyperthermia activates ion channels that negatively affect fetal development.
Open Access
The Role of Neural Crest Cells in Vertebrate Cardiac Outflow Development
(2014) Alonzo-Johnsen, Martha
Throughout vertebrate evolution, the cardiac outflow vasculature has changed from a branchial arch system to a systemic and pulmonary circulatory system. However, all vertebrate hearts and outflow tracts still develop from a single heart tube. In the chick and mouse, cardiac neural crest cells divide the single outflow tract into the aorta and pulmonary arteries. Additionally, cardiac neural crest cells provide the smooth muscle of the aortic arch arteries, help to remodel the aortic arch arteries into asymmetrical structures, and contribute cardiac ganglia. I review the major contributions of cardiac neural crest cells to the outflow vasculature of the chick and mouse and apply this information to study cardiac neural crest cell contributions to vertebrates that lack a divided circulatory system. I re-evaluate the role of cardiac neural crest cells in zebrafish vasculature and find that these cells do contribute to the gill arch arteries, the ventral aorta and cardiac ganglia, but they do not contribute to myocardium. I also study the outflow tract development of the turtle Trachemys scripta to understand the process of outflow septation in a vertebrate that has a divided outflow tract but an incomplete division of the ventricle. I compare the chick outflow tract to the turtle. The formation of the proximal versus distal cushions and the appearance of smooth muscle cells within the distal cushions of the turtle are very similar to the cushion position and cell types within the cushions of the chick. In the chick, the smooth muscle positive cells in the distal cushions are derived from cardiac neural crest cells. I hypothesize that cardiac neural crest cells are also responsible for the outflow tract septation of reptiles. These results demonstrate that the pattern of cardiac neural crest cell contribution to vertebrate vasculature remains predictable and consistent, enabling future studies to focus on changes in vascular patterning caused by cardiac neural crest cells among different vertebrate lineages.
Open Access
The secreted metalloprotease ADAMTS20 is required for melanoblast survival.
(PLoS Genet, 2008-02-29) Silver, Debra L; Hou, Ling; Somerville, Robert; Young, Mary E; Apte, Suneel S; Pavan, William J
ADAMTS20 (Adisintegrin-like and metalloprotease domain with thrombospondin type-1 motifs) is a member of a family of secreted metalloproteases that can process a variety of extracellular matrix (ECM) components and secreted molecules. Adamts20 mutations in belted (bt) mice cause white spotting of the dorsal and ventral torso, indicative of defective neural crest (NC)-derived melanoblast development. The expression pattern of Adamts20 in dermal mesenchymal cells adjacent to migrating melanoblasts led us to initially propose that Adamts20 regulated melanoblast migration. However, using a Dct-LacZ transgene to track melanoblast development, we determined that melanoblasts were distributed normally in whole mount E12.5 bt/bt embryos, but were specifically reduced in the trunk of E13.5 bt/bt embryos due to a seven-fold higher rate of apoptosis. The melanoblast defect was exacerbated in newborn skin and embryos from bt/bt animals that were also haploinsufficient for Adamts9, a close homolog of Adamts20, indicating that these metalloproteases functionally overlap in melanoblast development. We identified two potential mechanisms by which Adamts20 may regulate melanoblast survival. First, skin explant cultures demonstrated that Adamts20 was required for melanoblasts to respond to soluble Kit ligand (sKitl). In support of this requirement, bt/bt;Kit(tm1Alf)/+ and bt/bt;Kitl(Sl)/+ mice exhibited synergistically increased spotting. Second, ADAMTS20 cleaved the aggregating proteoglycan versican in vitro and was necessary for versican processing in vivo, raising the possibility that versican can participate in melanoblast development. These findings reveal previously unrecognized roles for Adamts proteases in cell survival and in mediating Kit signaling during melanoblast colonization of the skin. Our results have implications not only for understanding mechanisms of NC-derived melanoblast development but also provide insights on novel biological functions of secreted metalloproteases.