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 (reviewed in Muppirala et al., 2020).

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. One of these mutants, stl159, appears to disrupt the muscle environment of developing neurons and glia specifically in the peripheral nervous system. We found that these mutants have nerve pathfinding defects because a transcription factor in muscle, tcf15, is disrupted in stl159 (Limbach et al., 2022). We hypothesize that these muscle-derived factors are necessary for the interaction of neurons and glia during nerve development. The stl159 mutant is the focus of an 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).

Training in the Petersen Lab

Students in the Petersen lab may be trained in the following techniques:

- Zebrafish husbandry and aquaculture
- Molecular biology including PCR, restriction analysis, in vitro transcription
- Microinjection of nucleic acids, including CRISPR/Cas9, into zebrafish embryos
- In situ hybridization and immunostaining
- Pharmacological treatment of zebrafish embryos and larvae
- Brightfield and fluorescent microscopy of mounted fixed tissue
- In vivo live timelapse imaging of developing neurons and glia
- Primary cell culture of zebrafish neurons and glia
- Preparation of samples for transmission electron microscopy
- Micrograph analysis, quantification, and statistical analysis
- Computational approaches for genomic and mRNA-seq analysis

In addition, Petersen lab members are expected to regularly communicate their work orally and in writing. Students present at lab meetings, in course settings, and at regional or national conferences. Students are also expected to regularly read the scientific literature and explore online resources to develop their ideas.

All students working with zebrafish are required to complete CITI training, read and sign the IACUC and Zebrafish Facility Standard Operating Procedure protocols, and receive in-person training with Dr. Petersen prior to any work with the animals.

If you are interested in working in the Petersen lab, contact Prof. Petersen to discuss your options. Please note that students generally do not enroll in NEUR/BIOL 385 their first semester in the lab.

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