The virus entered the developing embryos where it over-expressed Alx3 in the melanocytes. Using ultrasound-guided injections, the researchers introduced a lentivirus carrying the Alx3 gene into pregnant mice.
To further probe the function of the gene, the researchers over- and under-expressed it in lab mice and in cell culture, respectively. They discovered that ALX3, a transcription factor, binds to the promoter and represses MITF, a known regulator of melanocyte differentiation. To figure that out, the researchers conducted protein-DNA binding assays to identify the sections of DNA to which the ALX3 protein could bind. The gene had not been implicated in pigmentation before, so the researchers weren’t sure how the gene was affecting mouse hair color. “It looks like what happened is that Alx3 has been co-opted from its role in making light-colored bellies, and now it’s expressed where the stripe is going to form,” explained Hoekstra. When they compared the expression of Alx3 in the African striped mouse and in the regular lab mouse, they found that all mice express Alx3 on their bellies, but the African striped mouse also expresses Alx3 in a striped pattern on its back. The team identified a gene called Alx3 that was highly expressed in the light colored stripe but not in the dark-haired areas.
If expression with chipmunk basic program skin#
To figure out which genes were involved, Mallarino and colleagues used RNA sequencing to measure all the genes that were activated in the skin in the light colored stripe compared to those in the skin that grew darker hair. The melanocytes that fail to differentiate cannot produce pigment, thus leading to light colored hair. He found that the pigment producing cells in the skin, called melanocytes, failed to differentiate in regions that corresponded to the location of the light-colored stripe. To investigate how the African striped mouse got its stripes, Ricardo Mallarino, a postdoctoral fellow in Hoekstra’s lab, first looked at how the stripes form during mouse embryogenesis. “We are working on a non-model organism that is closely related to a model, so we can get the best of both worlds,” Hoekstra explained. In addition, the wild mice are closely related to lab mice, for which a variety of genetic and genomic tools are available. HHMI Investigator Hopi Hoekstra of Harvard University studies the development and evolution of stripe patterns in wild mice because these stripes may play an important role in helping the mice escape predators.
How animal color patterns develop and evolve is a longstanding question in developmental biology. The same gene also determines the stripe pattern of North American chipmunks, and the similar stripe patterns evolved independently in these two groups of animals, researchers report in this week’s issue of Nature. A gene called Alx3 blocks the differentiation of pigment-producing cells in the skin of the African striped mouse, thus generating the mouse’s characteristic light-colored stripes, a new study shows.