Comet Calendar, The Official Event Calendar for UT Dallas en-us This week's events for Natural Sciences & Mathematics at UT Dallas Cecil H. and Ida Green Distinguished Lecture Presents: Dr. Thomas Maniatis, Chairman Department of Biochemistry & Molecular Biophysics, Columbia University, New York, NY Friday, May 6
(3:45 p.m. - 5 p.m.)

The Generation and Function of Single Cell Diversity in the Mammalian Brain

The ability of individual neurons to distinguish between self and non-self is a fundamental requirement for normal neural circuit assembly in the developing mammalian brain. Recent studies have shown that three tandem, closely linked gene clusters encoding the protocadherin (Pcdh) a, b and g cell surface proteins play a key role in neuronal self-recognition and brain wiring during mouse development.  

The unique genomic organization of the Pcdh gene clusters, and a mechanism of stochastic promoter choice leads to the generation of high levels of Pcdh diversity in individual neurons. Stochastic promoter choice has been shown to involve long-range DNA looping between distal transcriptional enhancers and individual Pcdh promoters. The CTCF/cohesin complex, which binds to both the Pcdh enhancers and promoters, is required for both DNA looping and Pcdh gene expression. 

Pcdh diversity is further expanded by the random combinatorial assembly of cis-dimers in individual neurons, which engage in highly specific homophilic interactions at the cell surface.  Cell aggregation and structural studies of Pcdh proteins have identified the key amino acid residues required for cis-dimerization and trans-homophilic interactions. Biophysical studies in conjunction with atomic structures have shown that Pcdh proteins form unique anti-parallel trans-dimers, which could form a Pcdh lattice between apposing cell surfaces of interacting neurons. This proposed lattice would increase the specificity and strength of Pcdh homophilic interactions.

Molecular genetic studies in the mouse have shown that the clustered Pcdhs are required for dendritic self avoidance in retinal starburst amacrine cells and Purkinje cells.  Recent studies of the role of Pcdhs in olfactory sensory neuron wiring, using both dominant gain of function and loss of function approaches, have shown that Pcdhs are required for the formation of glomeruli in the olfactory bulb, and that individual Pcdh gene clusters (a, b and g) display functional redundancy.

Human genetic studies of children with autism have identified DNA sequence variants that associate with the disease, and the Pcdh gene cluster is among the hundreds of genes where these variants have been identified.  Thus, the Pcdh gene cluster plays an important role in brain wiring, and Pcdh mutations may contribute to neurological diseases in humans.

(2 p.m.)

All Faculty Are Invited to the Final Examination of


Blake A. Wilson

Graduate Program in Chemistry

May 9, 2016, 2:00 p.m. in SLC 1.102


Title of Dissertation:



Student’s Supervising Committee:

Steven O. Nielsen, Chair

Gregg R. Dieckmann

Lev D. Gelb

Jie Zheng