Defects in ErbB-Dependent Establishment of Adult Melanocyte Stem Cells Reveal Independent Origins for Embryonic and Regeneration Melanocytes

Adult stem cells are responsible for maintaining and repairing tissues during the life of an organism. Tissue repair in humans, however, is limited compared to the regenerative capabilities of other vertebrates, such as the zebrafish (Danio rerio). An understanding of stem cell mechanisms, such as how they are established, their self-renewal properties, and their recruitment to produce new cells is therefore important for the application of regenerative medicine. We use larval melanocyte regeneration following treatment with the melanocytotoxic drug MoTP to investigate these mechanisms in Melanocyte Stem Cell (MSC) regulation. In this paper, we show that the receptor tyrosine kinase, erbb3b, is required for establishing the adult MSC responsible for regenerating the larval melanocyte population. Both the erbb3b mutant and wild-type fish treated with the ErbB inhibitor, AG1478, develop normal embryonic melanocytes but fail to regenerate melanocytes after MoTP-induced melanocyte ablation. By administering AG1478 at different time points, we show that ErbB signaling is only required for regeneration prior to MoTP treatment and before 48 hours of development, consistent with a role in establishing MSCs. We then show that overexpression of kitla, the Kit ligand, in transgenic larvae leads to recruitment of MSCs, resulting in overproliferation of melanocytes. Furthermore, kitla overexpression can rescue AG1478-blocked regeneration, suggesting that ErbB signaling is required to promote the progression and specification of the MSC from a pre–MSC state. This study provides evidence that ErbB signaling is required for the establishment of adult MSCs during embryonic development. That this requirement is not shared with the embryonic melanocytes suggests that embryonic melanocytes develop directly, without proceeding through the ErbB-dependent MSC. Moreover, the shared requirement of larval melanocyte regeneration and metamorphic melanocytes that develops at the larval-to-adult transition suggests that these post-embryonic melanocytes develop from the same adult MSC population. Lastly, that kitla overexpression can recruit the MSC to develop excess melanocytes raises the possibility that Kit signaling may be involved in MSC recruitment during regeneration

Gender-stratified gene and gene-treatment interactions in smoking cessation

We conducted gender-stratified analyses on a systems-based candidate gene study of 53 regions involved in nicotinic response and the brain-reward pathway in two randomized clinical trials of smoking cessation treatments (placebo, bupropion, transdermal an

Plasticity in Resource Allocation and Nitrogen-Use Efficiency in Riparian Vegetation: Implications for Nitrogen Retention

In this work, we summarize our current understanding of the function of riparian zones and describe an investigation of changes in the production per unit nitrogen (N) taken up, or nitrogen-use efficiency (NUE) and resource allocation of a riparian shrub in response to changes in N availability. Empirical work included measuring leaf %N and root-to-shoot ratios (R:S) of individual riparian shrubs (Baccharis salicifolia, or seepwillow) growing at a range of N availabilities in the field and growing in fertilized and unfertilized plots in a field fertilization experiment. In both observational and experimental work, N availability was related positively to %N of plant tissues and negatively to R:S. We used a simulation model to investigate feedbacks between seepwillow responses to and effects on N availability. In the model, plasticity in resource allocation and NUE in response to changes in N led to lower productivity at low N supply and higher productivity and lower retention at high N supply than was observed in plants constrained to a constant %N and R:S. Furthermore, uptake became relatively more important as a retention mechanism when plants responded to high N supply. These feedbacks could have significant effects on N retention by riparian zones in watersheds receiving large fertilizer inputs of N or on ecosystems exposed to high rates of atmospheric N deposition