Investigating how neurons respond and recover after injury
The Thompson-Peer lab explores how neurons recover from injury in vivo, and how this process is similar to and different from normal development.
At the most fundamental level, a neuron receives information along dendrites, and sends information down an axon to synaptic contacts. Dendrites can be injured by traumatic brain injury, stroke, and many forms of neurodegeneration, yet while the factors that control axon regeneration after injury have been extensively studied, we know almost nothing about dendrite regeneration. Our long term research goal is to understand the cellular mechanisms of dendrite regeneration after injury.
Our previous work found that the sensory neurons in the fruit fly Drosophila peripheral nervous system exhibit robust regeneration of dendrites after injury and used this system to explore central features of dendrite regeneration in developing animals, young adults, and aging adults. We have observed that after injury, neurons regrow dendrites that recreate some features of uninjured dendrites, but are unable to reconstruct an entire arbor that perfectly mimics an uninjured neuron. Moreover, there are mechanistic differences between the outgrowth of uninjured neurons versus the regeneration of dendrites after injury: dendrite regeneration is uniquely dependent on neuronal activity, ignores cues that constrain and pattern normal dendrite outgrowth, and confronts a mature tissue environment that is different from what a developing neuron would encounter. These challenges are significantly exacerbated when neurons in aging animals attempt to recover from injury.
Current and future projects will deepen our knowledge about dendrite regeneration to create a new framework for understanding how neurons recover from injury in both young and aging animals.
Thompson-Peer KL. (2020). Casein Kinase 1δ Triggers Giant Ankyrin Expression. Developmental Cell. 2020 Jan 6: 52(1):4-5. doi: 10.1016/j.devcel.2019.12.012. Preview for “Casein Kinase 1δ Stabilizes Mature Axons by Inhibiting Transcription Termination of Ankyrin”, same issue.
Thompson-Peer KL. (2020). Casein Kinase 1δ Triggers Giant Ankyrin Expression. Developmental Cell. 2020 Jan 6: 52(1):4-5. doi: 10.1016/j.devcel.2019.12.012. Preview for “Casein Kinase 1δ Stabilizes Mature Axons by Inhibiting Transcription Termination of Ankyrin”, same issue. Yadav S, Younger S, Zhang L, Thompson-Peer KL, Li Y, Jan LY, Jan YN (2019). Glial ensheathment of the somatodendritic compartment regulates sensory neuron structure and activity. PNAS. 2019 Feb 25 pii: 201814456. doi: 10.1073/pnas.1814456116. PMID: 30804200.
Song Y, Li D, Farrelly O, Miles L, Li F, Kim SE, Lo TY, Wang F, Li T, Thompson-Peer KL, Gong J, Murthy SE, Coste B, Yakubovich N, Patapoutian A, Xiang Y, Rompolas P, Jan LY, Jan YN. (2019). The mechanosensitive ion channel Piezo inhibits axon regeneration. Neuron. 2019 Feb 15. pii: S0896-6273(19)30077-7. doi: 10.1016/j.neuron.2019.01.050. PMID: 30819546.
DeVault L, Li T, Izabel S, Thompson-Peer KL, Jan LY, Jan YN. (2018). Dendrite regeneration of adult Drosophila sensory neurons diminishes with aging and is inhibited by epidermal-derived matrix metalloproteinase 2.Genes & Development. 2018 Mar 1;32(5-6):402-414. doi: 10.1101/gad.308270.117. PMID: 29563183.
Pym E, Sasidharan N, Thompson-Peer KL, Simon DJ, Anselmo A, Sadreyev R, Hall Q, Nurrish S, and Kaplan JM. (2017).Shank is a dose-dependent regulator of Cav1 calcium current and CREB target expression. eLife. 2017 May 6;6. pii: e18931. doi: 10.7554/eLife.18931. PMID: 28477407.
Lin C, Yao E, Zhang K, Jiang, X, Croll S, Thompson-Peer KL, and Chuang PT. (2017).YAP is essential for mechanical force production and epithelial cell proliferation during lung branching morphogenesis. eLife. 2017 Mar 21;6. pii: e21130. doi: 10.7554/eLife.21130. PMID: 28323616.
Thompson-Peer KL, DeVault L, Li T, Jan LY, and Jan YN. (2016). In vivo dendrite regeneration after injury is different from dendrite development.Genes & Development. 2016 Aug 1; 30(15): 1776-89. doi: 10.1101/gad.282848.116. PMID: 27542831. **Cover article**
Rumpf S, Bagley JA, Thompson-Peer KL, Zhu S, Gorczyca D, Beckstead RB, Jan LY, and Jan YN. (2014). Drosophila Valosin-Containing Protein is required for dendrite pruning through a regulatory role in mRNA metabolism. PNAS. 2014 May 20;111(20):7331-6. doi:10.1073/pnas.1406898111. PMID: 24799714.
Thompson-Peer KL*, Bai J*, Hu Z, Kaplan JM. (2012). HBL-1 patterns synaptic remodeling in C. elegans. Neuron. 2012 Feb 9; 73(3):453-65. doi: 10.1016/j.neuron.2011.11.025. PMID: 22325199.
Simon DJ*, Madison JM*, Conery AL, Thompson-Peer KL, Soskis M, Ruvkun GB, Kaplan JM, Kim JK. (2008). The microRNA miR-1 regulates a MEF-2-dependent retrograde signal at neuromuscular junctions. Cell. 2008 May 30; 133(5):903-15. doi: 10.1016/j.cell.2008.04.035. PMID:18510933.
Huang Z*, Yazdani U*, Thompson-Peer KL, Kolodkin AL, Terman JR. (2007). Crk-associated substrate (Cas) signaling protein functions with integrins to specify axon guidance during development. Development. 2007 Jun; 134(12):2337-47. doi: 10.1242/dev.004242. PMID:17537798.
Kantor DB, Chivatakarn O, Peer KL, Oster SF, Inatani M, Hansen MJ, Flanagan JG, Yamaguchi Y, Sretavan DW, Giger RJ, Kolodkin AL. (2004). Semaphorin 5A is a bifunctional axon guidance cue regulated by heparan and chondroitin sulfate proteoglycans. Neuron. 2004 Dec 16; 44(6):961-75. doi: 10.1016/j.neuron.2004.12.002. PMID:15603739.