2. Genetic analysis of neural development and disease in the mouse |
We are using the genetic tools we created (see Section 4 ) to investigate a broad range of neurodevelopmental processes. For example, we previously uncovered mechanisms by which neurons acquire their morphology and prune excessive axons and dendrites. We are currently investigating the function of homologs of wiring specificity molecules we discovered in the fly olfactory system in wiring the mammalian brain (e.g., Fig. 3). We have also studied the roles of neuronal activity and competition in sculpting dendritic trees (e.g., Fig. 4). Finally, we have used genetic tools in combination with genomic and behavioral analyses to investigate neurobiological basis of a human neurodevelopmental disorder. |
|Fig. 3: Ten3 protein (red) is highly expressed in proximal CA1 and distal subiculum. Scale, 200 µm. Proximal CA1 axons are known to project selectively to distal subiculum. Ten3 regulates this precise projection through its matching expression in CA1 axons and subicular targets, and its ability to promote homophilic adhesion between Ten3 expressing cells. After Berns DS, DeNardo LA, Pederick DT & Luo L (2018) Nature 554:328–333. |
|Fig. 4: Neurotrophin signaling in competitive dendrite morphogenesis. Sparse TrkC–/– Purkinje cell (green) has reduced dendritic height, total branch number and length compared to a neighboring TrkC+/– cell (yellow). Visualized by the MADM method. Dotted line, pia surface where normal Purkinje cell dendrite trees terminate. Scale bar, 100 µm. After Joo W, Hippenmeyer S & Luo L (2014) Science 346:626-629. |
Nakayama AY, Harms, MB & Luo L (2000) Small GTPases Rac and Rho in the maintenance of dendritic spines and branches in hippocampal pyramidal neurons. J Neurosci 20: 5329-5338.
Billuart P, Winter CG, Maresh A, Zhao X & Luo L (2001) Regulating axon branch stability: the role of p190 RhoGAP in repressing a retraction signaling pathway. Cell 107: 195-207
Ng J, Nardine T, Harms M, Tzu J, Goldstein A, Sun Y, Dietzl G, Dickson BJ & Luo L (2002) Rac GTPases control axon growth, guidance and branching. Nature 416: 442-447
Watts RJ, Hoopfer ED & Luo L (2003) Axon pruning during Drosophila metamorphosis: evidence for local degeneration and requirement of the ubiquitin-proteasome system. Neuron 38:871-885
Watts RJ, Schuldiner O, Perrino J, Larsen C & Luo L (2004) Glia engulf degenerating axons during developmental axon pruning. Curr Biol 14:678-684.
Hoopfer ED, McLaughlin T, Watts RJ, Schuldiner O, O'Leary DDM & Luo L (2006) Wlds protection distinguishes axon degeneration following injury from naturally-occurring developmental pruning. Neuron 50:883-895.
Espinosa JS, Wheeler DG, Tsien RW & Luo L (2009) Uncoupling dendrite growth and patterning: Single cell knockout analysis of NMDA receptor 2B. Neuron 62:205-217.
Joo W, Hippenmeyer S & Luo L (2014) Dendrite morphogenesis depends on relative levels of NT-3/TrkC signaling. Science 346:626-629.
DeNardo LA*, Berns DS*, DeLoach K & Luo L (2015) Connectivity of mouse somatosensory and prefrontal cortex examined with trans-synaptic tracing. Nat Neurosci 18:1687-1697.
Huang WH*, Guenthner CJ*, Xu J*, Nguyen T, Schwarz LA, Wilkinson AW, Gozani O, Chang HY, Shamloo M & Luo L (2016) Molecular and neural functions of Rai1, the causal gene for Smith-Magenis syndrome. Neuron 92:392-406.
Berns DS, DeNardo LA, Pederick DT & Luo L (2018) Teneurin-3 controls topographic circuit assembly in the hippocampus. Nature 554:328-333.
Huang WH, Wang DC, Allen WE, Klope M, Hu H, Shamloo M & Luo L (2018). Early adolescent Rai1 reactivation reverses transcriptional and social interaction deficits in a mouse model of Smith-Magenis syndrome. Proc Natl Acad Sci USA 115:10744-10749.
* co-first authors
See publications for complete list and PDFs.