Biomedical subjects
Publications and source records attributed to Wendy Ching.
The Wnt family of signaling proteins mediates cell-cell communication during development. In this issue of Cell, Bänziger et al. (2006) and Bartscherer et al. (2006) identify Wntless/Evi, a multipass transmembrane protein in the secretory pathway of Wnt-producing cells that promotes Wnt secretion.
Glatiramer acetate (GA) is a disease-modifying therapy for relapsing-remitting multiple sclerosis (RRMS) with several putative mechanisms of action. Currently, there is paucity of in vivo human data linking the well-established peripheral immunologic effects of therapy with GA to its potential effects inside the central nervous system (CNS). Brain proton magnetic resonance spectroscopy (MRS) allows in vivo examination of axonal integrity by quantifying the resonance intensity of the neuronal marker N-acetylaspartate (NAA). In a pilot study to investigate the effect of GA on axonal injury, we performed combined brain magnetic resonance imaging (MRI) and MRS studies in 18 treatment naïve RRMS patients initiating therapy with GA at baseline and annually for two years on therapy. A small group of four treatment naïve RRMS patients, electing to remain untreated, served as controls. NAA/Cr was measured in a large central brain volume of interest (VOI) as well as the normal appearing white matter (NAWM) within the VOI. After two years, NAA/Cr in the GA-treated group increased significantly by 10.7% in the VOI (2.17 +/- 0.26 versus 1.96 +/- 0.24, P = 0.03) and by 71% in the NAWM (2.23 +/- 0.26 versus 2.08 +/- 0.31, P = 0.04). In the untreated group, NAA/Cr decreased by 8.9% at two years in the VOI (2.01 +/- 0.16 versus 1.83 +/- 0.21, P = 0.03) and 8.2% in the NAWM (2.07 +/- 0.24 versus 1.90 +/- 0.29, P = 0.03). Our data shows that treatment with GA leads to axonal metabolic recovery and protection from sub-lethal axonal injury. These results support an in situ effect of GA therapy inside the CNS and suggest potential neuroprotective effects of GA.
Neural crest cells migrate segmentally through the rostral half of each trunk somite due to inhibitory influences of ephrins and other molecules present in the caudal-half of somites. To examine the potential role of Notch/Delta signaling in establishing the segmental distribution of ephrins, we examined neural crest migration and ephrin expression in Delta-1 mutant mice. Using Sox-10 as a marker, we noted that neural crest cells moved through both rostral and caudal halves of the somites in mutants, consistent with the finding that ephrinB2 levels are significantly reduced in the caudal-half somites. Later, mutant embryos had aberrantly fused and/or reduced dorsal root and sympathetic ganglia, with a marked diminution in peripheral glia. These results show that Delta-1 is essential for proper migration and differentiation of neural crest cells. Interestingly, absence of Delta-1 leads to diminution of both neurons and glia in peripheral ganglia, suggesting a general depletion of the ganglion precursor pool in mutant mice.