Dr. Hannes E. Buelow

Assistant Professor

Ullmann Building
Room 807
phone: (718) 430-3621
fax: (718) 430-8778
email: hbuelow@aecom.yu.edu

 

Genetics of Nervous System Development

My lab uses the small nematode C. elegans as a genetic model to understand how growing axons navigate the extracellular space in order to connect to their appropriate partners. The extracellular space is filled with a complex mixture of proteins and proteoglycans, e.g. heparan sulfate (HS) proteoglycans which are a particular focus of the lab. HS is a polysaccharide that displays enormous molecular diversity through modifications of the sugar residues. We have shown that distinct modification patterns in HS serve specific functions during nervous system development leading us to formulate the 'HS code' hypothesis. We propose that defined combinations of modifications in the sugars of HS contain information and generate a molecular map that helps shaping the nervous system. Our goal is to decipher the information contained in HS, determine the factors that create and modulate it and describe the genes that respond to it.

In a related project we are investigating a pathological dimension of HS by studying Kallmann Syndrome, a human genetic disease with specific neural targeting defects. Using C. elegans, we have shown that kal-1, the nematode orthologue of the gene mutated in human Kallmann patients, has a role in axon branching and requires HS with specific modifications for these functions. Our goal here is to understand how KAL-1 functions on a molecular level during disease and development.

In summary, our studies are directed towards a better understanding of how heparan sulfate and its modifications (the 'HS code') functions during development and disease of the nervous system.

Selected Publications

Bülow, H.E., Berry, K.L., Topper, L.H., Peles, O. and Hobert, O. (2002). Heparan sulfate proteoglycan-dependent induction of axon branching and axon misrouting by the Kallmann syndrome gene kal-1. PNAS 99(9): 6346-6351.

Hobert, O. and Bülow, H. (2003) Development and maintenance of neuronal architecture at the ventral midline: New lessons from C. elegans. Curr. Op. Neurobiol. 13(1):70-78.

Bülow, H.E. and Hobert, O. (2004) Differential sulfations and epimerization define heparan sulfate specificity in nervous system development. Neuron 41:723-736.

Bülow, H.E. Boulin, T., and Hobert, O. (2004) Differential functions of the C. elegans FGF receptor in axon outgrowth and maintenance of axon position. Neuron 42:367-374.

Bülow, H.E.and Hobert, O. (2006) The Molecular Diversity of Glycosaminoglycans shapes Animal Development. Ann. Rev. Cell. Dev. Biol. 22:375-407.