Yimin Zou, Ph.D. Associate Professor Department of Neurobiology,    Pharmacology, and Physiology Committee on Neurobiology

Molecular mechanisms of axon guidance in development.

 My laboratory studies the molecular mechanisms of axon guidance in vertebrate development. We use a combination of molecular, biochemical, embryological and genetic approaches to identify novel axon guidance molecules, study the in vivo function of guidance cues and understand their signaling mechanisms in wiring our nervous system. 

The vertebrate nervous system is wired along the dorsoventral and anteroposterior body axes. Although relatively more is known about the dorsal-ventral patterning of axons, little is known about the mechanisms of anterior-posterior axon patterning. The anterior-posterior axons are essential for sending information along the A-P axis, for example connecting the spinal cord with the brain. Sensory signals ascend from the spinal cord to the brain and motor commands descend from the brain to the spinal cord. 

One major focus in our lab is the axon patterning in the anteroposterior neuraxis during the development of the vertebrate central nervous system.  Initially, our primary model system is the spinal cord commissural axons, which cross the midline at the floor plate of the developing spinal cord and turn immediately rostral along the anteroposterior axis after midline crossing.  We use expression cloning, protein purification, and candidate gene approaches to identify the cues that play a role in the longitudinal growth of commissural axons. We then use in vitro explant assays to assess the function of guidance molecules and test the in vivo function of axon guidance molecules using transgenic mice or knockout mice. Multiple axons often respond to the same guidance cues. We will test whether the same sets of cues regulate anterior-posterior patterning of other ascending and descending pathways.
   

References

Yaobo Liu, Jun Shi, Chin-Chun Lu, Zheng Bei Wang, Anna I. Lyuksyutova, Xuejun Song and Yimin Zou.  2005  Ryk-medicated Wnt repulsion regulates posterior-directed growth of corticospinal tract.  Nature Neuroscience Sep 8(9):1151-9.

Adam Schmitt, Jun Shi, Alex Wolf, Chin-Chun Lu, Leslie A. King and Yimin Zou.  2005  Wnt-Ryk signaling mediates medial-lateral retinotectal topographic mapping. Nature Article (online advance publication November 9, 2005. Doi:10:138/nature04334).

Lee Fradkin, Gian Garriga, Patricia C. Salinas, John Thomas, Xiang Yu and Yimin Zou.  2005  Wnt signaling in neural circuit development (minireview) J Neuroscience. 25(45):10376-10378.

Yimin Zou.  2004. Wnts signaling in axon guidance (review). Trends in Neuroscience, 27(9): 528-532.

Yimin Zou, Florian Engert, Huizhong W. Tao.  2004  The assembly of neural circuits (meeting report).  Neuron, 43(2): 159-163.

Anna I. Lyuksyutova,, Chin-Chun Lu, Nancy Milanesio, Leslie A. King, Nini Guu, Yanshu Wang, Jeremy Nathans, Marc Tessier-Lavigne and Yimin Zou. 2003  Anterior-posterior guidance of commissural axons by Wnt-frizzled signaling. Science, 302:1984-1988.

Elke Stein, Yimin Zou, Mu-ming Poo, and Marc Tessier-Lavigne.  2001. Netrin-1 binds DCC to stimulate axon outgrowth and turning independent of adenosine A2B receptor activation. Science, 291(5510):1976-82.

Yimin Zou, Esther Stoeckli, Hang Chen, and Marc Tessier-Lavigne.  2000  Squeezing axons out of the gray matter: A role for slit and semaphorin proteins from midline and ventral spinal cord.  Cell, 102:363-375. 

Hang Chen, Anil Bagri, Joel A. Zupicich, Yimin Zou, Esther Stoeckli, Samuel J. Pleasure, Daniel H. Lowenstein, William C. Skarnes, Alain Chédotal, and Marc Tessier-Lavigne.  2000.  Neuropilin-2 regulates the development of select cranial and sensory nerves and hippocampal mossy fiber projections.  Neuron, 25(1): 43-56. 

Hai-Chien Kuo, Ju Chen, Pilar Ruiz-Lozano, Yimin Zou, Mona Nemer and Kenneth R. Chien. 1999  Control of segmental expression of the cardiac-restricted ankyrin repeat protein gene by distinct regulatory pathways in murine cardiogenesis. Development, 126: 4223-4234. 

Yimin Zou,  Sylvia Evans, Ju Chen, Hai-Chien Kuo, Richard P. Harvey, and Kenneth R. Chien.  1997  CARP, a cardiac ankyrin repeat protein, is downstream in the Nkx2-5  homeobox gene pathway. Development, 124:793-804. 

Yimin Zou, and Kenneth R. Chien.  1995  EFIA/YB-1 is a component of cardiac HF-1A binding activity and positively regulates transcription of the myosin light chain-2v gene.  Mole. Cell. Biol, 15:2972-2982.