Zhen Huang

 

 

Genetic and molecular analysis of cortical laminar assembly and dendrite development

E-mail: z.huang@neurology.wisc.edu

Research Strengths: Molecular Neuroscience; Development: Plasticity and Repair

My lab is interested in several aspects of the development of the cerebral cortex. We are interested in how the different levels of organization in the cortex (from global to cellular and synaptic) arise during normal development and how they are affected in and contribute to human diseases. To investigate how the laminar organization of the cortex arises, we focus on a group of early-born neurons named the Cajal-Retzius (C-R) cells, which are best known for their expression of the key signaling molecule Reelin. Using mouse genetics and slice culture approaches, we are addressing several fundamental questions about the C-R cells: 1) How are the C-R cells guided to their specific destinations (the marginal zone) in the cortex? 2) What are the functions of the C-R cells in cortical neuronal cell fate determination and cortical laminar organization? 3) What is the precise role of the C-R cells in Reelin signaling? 4) What is their role in the development of cortical dysplasia?

We are also interested in how other levels of cortical organization develop, e.g., we are interested in how the different types of neurons in the brain develop their distinct and stereotyped patterns of dendritic morphology and how these contribute to the development of neuronal connectivity. Currently we are focusing on the roles of several cell division genes in this process. We are in particular interested in genes involved in the determination of spindle orientation during cell division and are using mouse genetics as well as neuronal culture to address their functions in dendrite development. We aim to address several questions in this area: 1) Do the molecular mechanisms that regulate microtubule (MT)-cortical interaction during cell division play a role in regulating dendrite development? 2) If so, how do these molecular interactions adapt for the development of the diverse dendrite patterns in the brain? 3) How may the distinct dendritic patterns of the different neuronal cell types contribute to the development of specific neuronal connectivity, and to the generation of specific innate or learned behavior? 4) How may defects in this pathway contribute to neurological diseases?

Lab Website:

http://www.neurology.wisc.edu/huang.html

Selected Publications:

• Huang, Z, K. Shimazu, N.H. Woo, K. Zang, U. Müller, B. Lu, and L.F. Reichardt. 2006. Distinct roles of the 1-class integrins at the developing and the mature hippocampal excitatory synapse. The Journal of Neuroscience 26: 11208-11219. [PDF]
• Huang, Z., K. Zang, and L.F. Reichardt. 2005. The origin recognition core complex regulates dendrite and dendritic spine development in postmitotic neurons. The Journal of Cell Biology 170: 527-535. [PDF]
• Graus-Porta, D., S. Blaess, M. Senften, A. Littlewood-Evans, C. Damsky, Z. Huang, P. Orban, R. Klein, J.C. Schittny, and U. Müller. 2001. 1-class integrins regulate the development of laminae and folia in the cerebral and cerebellar cortex. Neuron 31: 367-79. [PDF]
• Huang, Z., B-Z. Shilo, and S. Kunes. 1998. A retinal axon fascicle uses Spitz, an EGF receptor ligand, to construct a synaptic cartridge in the brain of Drosophila. Cell 95: 693–703. [PDF]
• Huang, Z. and S. Kunes. 1998. Signals transmitted along retinal axons in Drosophila: Hedgehog signal reception and the cell circuitry of lamina cartridge assembly. Development 125: 3753-3764. [PDF]
• Huang, Z. and S. Kunes. 1996. Hedgehog, transmitted along retinal axons, triggers neurogenesis in the developing visual centers of the Drosophila brain. Cell 86: 411-422. [PDF]