skip to content »

Molecular and Human Genetics

Houston, Texas

Department of Molecular and Human Genetics
Department of Molecular and Human Genetics
not shown on screen

Hugo J. Bellen, D.V.M., Ph.D.

Hugo J. Bellen, D.V.M., Ph.D.Professor, Department of Molecular and Human Genetics

Other Positions

Professor, Department of Neuroscience
Investigator, Howard Hughes Medical Institute
Professor and Director, Program in Developmental Biology

Education

M.B.A., University of Brussels, Belgium, 1976
D.V.M., University of Ghent, Belgium, 1983
Ph.D., University of California, Davis, 1986
Postdoc, University of Basel, Biozentrum, Switzerland, 1989

Research Interests

Genetic and molecular analysis of neurotransmitter release and nervous system development in Drosophila

Communication within the nervous system involves neurotransmitter release from synaptic vesicles that fuse with the presynaptic membrane following a calcium influx during an action potential. The biochemical and molecular events underlying neurotransmitter release and the trafficking of synaptic vesicles within the presynaptic terminal are currently being intensely investigated. We and others have shown that proteins implicated in neurotransmitter release in vertebrates have been extremely well conserved during evolution. Hence, it has been possible to isolate the Drosophila homologues of vertebrate proteins implicated in synaptic vesicle trafficking and to create mutations in the corresponding genes using a reverse genetic approach. The fruitfly, Drosophila, is an excellent model system to study synaptic transmission because the awesome power of genetics combined with the availability of several functional assays, including sophisticated electrophysiological and electron microscopy paradigms, allow us to describe the defects associated with these mutations. These studies combined with FM1-43 dye-uptake experiments allow us to determine when and where these proteins are precisely required in the synaptic vesicle cycle. Our laboratory presently focuses on VAP33 also named ALS8, a new Ca++ channel required for Endocytosis, as well as several novel proteins identified in forward genetic screens that affect endo and exocytosis.

To gain a more fundamental insight into the molecular mechanisms affecting the development of the nervous system, we have performed chemical and P-element mutagenesis screens to identify mutations that affect the development of the peripheral nervous system. More than 30 novel genes have presently been isolated. We are presently focusing on five genes that are implicated in Notch signaling or function in parallel to Notch signaling. The Notch pathway has been shown to play a seminal role in development and the fate of many cell lineages is controlled by Notch. Most proteins that mediate Notch signaling were first identified in Drosophila because they affect the development of the nervous system. Using chemical mutagenesis and a simple screening methodology we have been able to identify and map a number of new loci. These include Arp3, an actin binding protein, Ero1L, a protein required for disulfide bond formation, and rumi, a novel glucosyl transferase.

Adult Drosophila brain

Adult Drosophila brain labeled with synaptojanin (left) and synaptotagmin (right). Both are key components of the synaptic vesicle cycle (Verstreken et. al., 2003).

Selected Publications

  1. Rajan A, Tien A-C, Haueter C, Schulze KL, Bellen HJ (2009). The Arp2/3 complex and WASp are required for apical trafficking of Delta into microvilli during cell fate specification. Nat. Cell Biol. 11(7): 815-24. [Pub Med]
  2. Venken KJ, Schulze KL, Carlson JW, Pan H, He Y, Spokony R., Wang K, Koriabine M, de Jong PJ, White KP, Bellen HJ, Hoskins RA (2009). Versatile P(acman) BAC libraries for germ-line transformation studies in Drosophila melanogaster. Nat. Methods 6: 431-34. [Pub Med]
  3. Tsuda H, Han SM, Yang Y, Tong C, Lin YQ, Mohan K, Haueter C, Zoghbi A, Harati Y, Kwan J, Miller MA, Bellen HJ (2008). The amyotrophic lateral sclerosis 8 protein VAPB is cleaved, secreted, and acts as a ligand for Eph receptors. Cell 133(6): 963-77. [Pub Med]
  4. Zhai RG, Zhang F, Hiesinger PR, Cao Y, Haueter CM, Bellen HJ (2008). NAD synthase NMNAT acts as a chaperone to protect against neurodegeneration. Nature 452(7189): 887-91. [Pub Med]
  5. Acar M, Jafar-Nejad H, Takeuchi H, Rajan A, Ibrani D, Rana NA, Pan H, Haltiwanger RS, Bellen HJ (2008). Rumi is a CAP10 domain glycosyltransferase that modifies Notch and is required for Notch signaling. Cell 132(2): 247-58. [Pub Med]
  6. Venken KJ, He Y, Hoskins RA, Bellen HJ (2006). P[acman]: a BAC transgenic platform for targeted insertion of large DNA fragments in D. melanogaster. Science 314(5806): 1747-51. [Pub Med]
  7. Hiesinger PR, Fayyazuddin A, Mehta SQ, Rosenmund T, Schulze KL, Zhai RG, Verstreken P, Cao Y, Zhou Y, Kunz J, Bellen HJ (2005). The v-ATPase V0 subunit a1 is required for a late step in synaptic vesicle exocytosis in Drosophila. Cell 121(4): 607-20. [Pub Med]
  8. Verstreken P, Kjaerulff O, Lloyd TE, Atkinson R, Zhou Y, Meinertzhagen IA, Bellen HJ (2002). Endophilin mutations block clathrin-mediated endocytosis but not neurotransmitter release. Cell 109(1): 101-12. [Pub Med]
  9. Lloyd T, Atkinson R, Wu MN, Pennetta G, Bellen HJ (2002). HRS regulates endosome membrane invagination and tyrosine kinase receptor signaling in Drosophila. Cell 108(2): 261-9. [Pub Med]

More Publications (PubMed)

Contact Information

Hugo J. Bellen D.V.M., Ph.D.
Howard Hughes Medical Institute
Baylor College of Medicine
One Baylor Plaza, MS BCM235
Houston, TX, 77030, U.S.A.

Phone: 713-798-5272
Fax: 713-798-3694
E-mail:
Web site: Bellen Lab

E-mail this page to a friend