faculty research

Zhen Huang

Lab Location: MSC SMI 335, 1300 University (temp location: SMI 106)

Contact Info:
SMI 335
1300 University Ave.
Office Phone: 608.263.2469
Fax: 608.262.7306
Email: z.huang@neurology.wisc.edu
Publications: PubMed | selected publications
Faculty Profile: Dr. Huang

Research

The cerebral cortex is the site of higher cognitive function in the brain.  Its function depends critically on the intricate organization at several levels within the cortex.  This ranges from the global organization of neuronal cell bodies in the cortex (e.g., the formation of cortical layers), to the elaboration of distinct dendritic patterns by various types of neurons, and eventually to the formation of specific synaptic connections among the different types of neurons.  My lab is interested in several aspects of the development of the cerebral cortex.  We are particularly interested in how these different levels of organization in the cerebral cortex arise during normal development and how they are affected in and contribute to human diseases.  We are using several approaches including mouse genetics and in vitro tissue culture to address these questions.

Cortical laminar assembly:

To investigate how the laminar (and columnar) neuronal organization arises, we study mouse cortical development from its very early stage when the organization is beginning to be assembled.   We focus on a group of early-born neurons named the Cajal-Retzius (C-R) cells.  The C-R cells are a very unique group of neurons in that they are a born at the very beginning of cortical neurogenesis.  They appear to originate from several sources outside the cortex but invade the cortex just as it embarks on neurogenesis.  Once inside the cortex, the C-R cells occupy strategic positions in the most superficial layer of the emerging cortex (the marginal zone).  They express a very high level of Reelin, a secreted molecule critically required for normal neuronal migration in the cortex.  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 in the cortex?
2. What are the functions of the C-R cells in cortical neuronal fate determination and neuronal cell body organization?
3. What is the exact role that the C-R cells play in Reelin signaling?
4. What is their role in the development of cortical dysplasia?

Neuronal dendrite development:

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 dendritic patterns and how these contribute to the development of specific neuronal connectivity.  Since our previous data have implicated in this process genes normally involved in cell division, we are focusing on the roles of several cell division genes in dendrite development.  We are in particular interested in genes involved in determining spindle orientation during cell division and are using mouse genetics as well as neuronal cell culture systems to address their potential functions in dendrite development.  Through these efforts, we are aiming to address several key 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. How do these molecular interactions adapt for the development of the diverse dendrite patterns in the brain?
3. How may these distinct dendritic patterns contribute to the development of specific neuronal connectivity, and ultimately, to the generation of specific innate or learned behavior?

4)  How do defects in this pathway contribute to neurological diseases?

Figure 1

Figure 1.  The cerebral cortex develops from a thin layer of neuroepithelium in the forebrain, which contains numerous neuronal precursor cells, the radial glia (red), that span the entire developing cortical wall.  The Cajal-Retzius cells (green) are a unique population of early-born neurons that originate from outside the cortex and occupy strategic positions in the marginal zone, where they are believed to play a key role in orchestrating cortical development. 

Figure 2

Figure 2.  Different types of neurons in the brain develop distinct patterns of dendritic structures.  Shown here is a pyramidal neuron cultured in vitro for about 3 weeks.  It displays the characteristic pattern of process differentiation found in vivo, i.e., with the formation of a single axon (arrow) and multiple dendrites, which are decorated by numerous tiny protrusions termed dendritic spines (arrowheads).  These dendritic spines are the sites of the majority of synaptic contacts in our brain.

Figure 3

Figure 3.  in vitro neuronal culture offers an advantageous system for studying neuronal cell biology.  Shown here is a neuron cultured for about one week in vitro and transfected with Enhanced Green Fluorescent Protein (EGFP, green) gene. The cultured neurons undergo a similar process of differentiation as in vivo, with expression of genes such as the microtubule binding protein MAP2 (red).