Research in the Petersen Lab

See our full list of publications here.

Genetic regulation of nervous system development

Our lab is interested in identifying and characterizing the genes and molecules that are necessary to set up a properly functioning nervous system. In particular, we look at the development of glial cells in the central nervous system and periphery. Glial cells are essential for neuron health and signaling, and the loss of glial cells in humans results in debilitating neurological disorders like multiple sclerosis and Charcot-Marie-Tooth disease. We are especially interested in the ways that developing neurons and glia interact with each other and with the environment to create a properly patterned nervous system.

Why zebrafish?

Zebrafish are small, freshwater teleost fish that are relatively easy to raise in laboratory conditions. You may have even seen them at the pet store! We use zebrafish because they readily mate to produce many large, rapidly developing embryos that survive externally from the mother in a petri dish. These "fish in a dish" allow us to study genes controlling nervous system patterning more easily than in mammalian models, such as mice. Importantly, the major genetic regulators of nervous system development, from neurons to glia and the environments in which they develop, are conserved from zebrafish to humans. Therefore, we can define molecular mechanisms controlling development in zebrafish to learn how it might work in our own nervous systems.

Figure 1: Schematic of major myelinated axons in a zebrafish larvae. Central nervous system (CNS) axons are shown in red; peripheral nervous system (PNS) axons are blue. The anterior lateral line nerve (ALLn) and posterior lateral line nerve (PLLn) are readily observable nerves we use as a model for PNS development. Compass denotes dorsal (D)-ventral (V) and anterior (A)-posterior (P) axes. Figure adapted from D'Rozario, Monk, & Petersen 2017 (read it here).

Projects in the Petersen Lab

The Petersen Lab studies multiple zebrafish mutants with aberrant nervous system development. We have demonstrated that one of these mutants appears to disrupt the muscle environment of developing neurons and glia specifically in the peripheral nervous system (Limbach et al. 2022). We hypothesized that the tcf15 transcription factor in muscle is disrupted in this stl159 mutant, and that muscle-derived factors are necessary for the interaction of neurons and glia during nerve development. This study is the focus of a National Science Foundation CAREER Award in the Petersen lab.

Another mutant in our lab, stl93, has reduced neural and glial development in both the central nervous system (brain and spinal cord) as well as the periphery. We are characterizing stl93 mutants both phenotypically and genomically to understand the molecular basis of the phenotype.

We have also looked at pharmacological factors that can affect glial cell development. In a screen for small molecules that rescue myelination defects, we discovered that aporphine-class drugs are capable of activating Gpr126, a G protein-coupled receptor necessary for peripheral myelination (Bradley et al. 2019). Additional hits from this screen point us toward new genetic factors that mediate peripheral glial cell development.

Figure 2: stl159 mutants have disrupted PLLn expression of myelin basic protein (mbp, visualized with in situ hybridization in A-B) and Acetylated Tubulin (AcTub, visualized with immunostaining C-D). Note mispatterning of glial cells (mbp), axons (AcTub), and pigment cells (marked with asterisk).

Figure 3: Apomorphine restores PLLn mbp expression in gpr126 mutants. Note absence of mbp in gpr126 control-treated mutant (C) relative to wild-type sibling (WT in A), whereas treatment with 100 uM apomorphine increases mbp expression in the PLLn of the gpr126 mutant (D). Figure adapted from Bradley et al. 2019 (read it here).