Volker Hartenstein
email: volkerh@mcdb.ucla.edu
phone: (310) 206-7523
office: 559 Boyer Hall
lab: 559
homepage: http://www.mcdb.ucla.edu/Research/Hartenstein
Research Interests
Areas of Research
A. Neural development in Drosophila melanogaster.
1. We are focussing on the function of the adhesion molecules Drosophila E-cadherin homolog (DE-cad) and Fas (an Ig-like protein) during neuroblast formation, axonogensis and synapse formation in the embryonic and larval brain. Following the cloning of DE-cad, its phenotypic and expression analysis, we have generated constructs that allow us to overexpress normal and mutant DE-cad forms at specific times and locations during nervous system development.
Tepass, U., Gruszynski-de Feo, E., Haag, T.A., Omatyar, L., Török, T., and Hartenstein, V. (1996). shotgun encodes Drosophila E-cadherin and is preferentially required during cell rearrangement in the neuroectoderm and other morphogenetically active epithelia. Genes & Dev. 10, 672-685
Lekven, A., Tepass, U., Keshmeshian, M., Hartenstein, V. (1998) faint sausage encodes a novel member of the Ig superfamily required for cell movement and axonal pathfinding in the Drosophila nervous system. Development 125, 2747-2758
Haag, T., Prtina, N., Lekven, A.C., Hartenstein, V. (1999). Discrete steps in the morphogenesis of the Drosophila heart require faint sausage, shotgun/ DE-cadherin, and laminin A. Dev. Biol. 208, 56-69
2. Of special interest is the question of the dynamic regulation of DE-cad. Based on genetic evidence we hypothesize that the Drosophila EGF-receptor is crucially involved in this regulation. We use a genetic and biochemical approach to investigate this hypothesis.
Dumstrei, K., Nassif, C., Abboud, G., Aryai, A., Aryai, AR, Hartenstein, V. (1998) EGFR signaling is required for the differentation and maintenance of neural progenitors along the dorsal midline of the Drosophila embryonic head. Development 125, 3417- 3426
3. Using specific markers, we have initiated a "Drosophila brain mapping" project. The markers are expressed from embryonic stages onward in specific subsets of axon tracts. Other markers label glial cells and axon terminals. These structures are followed throughout larval stages into the adult brain and serve as "landmark" structure
Hartenstein, V., Tepass, U. and Gruszynski-de Feo, E. (1996). Proneural and neurogenic genes control specification and morphogenesis of stomatogastric nerve cell precursors in Drosophila. Dev. Biol. 173, 213-227
Younossi-Hartenstein, A., Nassif, C. and Hartenstein, V. (1996). Early neurogenesis of the Drosophila brain. J. Comp. Neur. 370: 313-329
Hartenstein, V. (1997) The development of the stomatogastric nervous system. Trends in Neurosci. 20, 421-427
Nassif, C., Noveen, A., and Hartenstein, V. (1998) Embryonic development of the Drosophila brain I. The pattern of pioneer tracts. J. Comp. Neur. 402, 10-31
Hartenstein, V., Nassif, C., and Lekven, A. (1998) Embryonic development of the Drosophila brain II. The glia cells of the brain. J. Comp. Neur.402, 32-48
4. A brain region of particular interest is the mushroom body (MB), the insect center for learning and memory formation. We have identified the homeobox gene eyeless (ey) to be expressed in the developing MB and required for its normal structure.
Noveen, A., Daniel, A., Hartenstein, V. (2000) The role of eyeless in the embryonic development of the Drosophila mushroom body Development 127, 3475-3488
B. Partitioning the fate map of the brain-comparison between Drosophila and vertebrates
The eye field in the anterior neural plate of vertebrates is the early embryonic domain that gives rise to forebrain and eye. The vertebrate eye field and the head ectoderm in the Drosophila embryo exhibit an amazing degree of similarity in terms of the fate map of different components of the visual system, and in the signaling pathways controlling this fatemap. Drosophila homologs of Shh (Hh), BMP4 (Dpp), as well as Pax6 (eyeless) and Six6 (sine oculis) and many other regulatory genes all function in the Drosophila embryonic head. Preliminary evidence shows that Dpp is secreted in the dorsal midline and forms a dorso-ventral gradient that specifies the different domains within the eye field. Hh is secreted at the lateral boundary of the eye field and may form a gradient that antagonizes the early Dpp gradient. We are reconstructing the details of the fate map of the Drosophila head, and study experimentally the function of the Hh and Dpp gradients in patterning the fatemap.
Rudolph, K., Liaw, G., Daniel, A., Green, P.J., Courey, A.J., Hartenstein, V., Lengyel, J. (1997). Complex regulatory region mediating tailless expression in early embryonic patterning and brain development. Development 124, 4297-4308
Nassif, C., Daniel, A., Lengyel, J.A., and Hartenstein, V. (1998) The role of morphogenetic cell death during embryonic head development of Drosophila Dev. Biol. 197, 170-186
Daniel, A., Dumstrei, K., Lengyel, J., Hartenstein, V. (1999) tailless and atonal control cell fate in the embryonic visual system. Development 126, 2945-2954
Lebestky, T., Chang, T., Hartenstein, V., Banerjee, U. (2000) Specification of Drosophila hematopoietic lineage by conserved transcription factors. Science 288, 146-149
C. Neural development in primitive invertebrates: platyhelminthes
One of the most astounding realizations of modern developmental biology is the high degree to which genes or even complete gene networks are conserved among all animal groups. Examples can be cited for virtually all fundamental developmental steps (e.g., establishment of body axes, gastrulation) and organ systems. In light of these findings the interest in comparative embryology as a basis for discussion of homologies between cells, tissues and organs has increased over the recent years. The fact that animals as divergent as flies and humans express regulatory genes such as eyeless , orthodenticle or the Hox genes implies that the common ancestor had these genes in its genetic repertoire; but what biological function did they serve? It is generally believed that the common ancestor of gastroneuralians ("protostomes") was a simple bilaterian organism with features such as a small acoelomate body, ciliated epidermis with underlying muscle layer, and a single gut opening. Many of these primitive features are conserved among the present day platyhelminths, a taxon that on the basis of morphological evidence has split early from the gastroneuralian (protostomian) line.
We have studied the normal development of representative of several flatworm taxa and are now focussing on two species that can be raised in the lab. PCR based cloning of homologs of genes involved in neural development of both Drosophila and vertebrates is under way.
Younossi-Hartenstein, A., Ehlers, U., Hartenstein, V. (2000) Embryonic development of the nervous system of the rhabdocoel flatworm Mesostoma lingua (Abildgaard, 1789). J. Comp. Neur. 416, 461-476
Hartenstein, V., Dwine, K. (2000). A new freshwater dalyellid flatworm, Gieysztoria superba sp. nov. (Dalyellidae: Rhabdocoela) from Southeast Queensland, Australia. Memoirs of the Queensland Museum 45, 381-383
Younossi-Hartenstein, A., Hartenstein, V. (2000a) The embryonic development of the dalyellid flatworm Gieysztoria superba .Int.J.Dev.Biol. (in press)
Younossi-Hartenstein, A., Hartenstein, V. (2000b) The embryonic development of the polyclad flatworm Imgogine mcgrathi Dev. Genes Evol. 210, 383-398
Hartenstein, V., Ehlers, U. (2000) The embryonic development of the rhabdocoel flatworm Mesostoma lingua. Dev. Genes Evol. 210, 399-415
Ramachandra, N.B., Ladurner, P., Jacobs, D. and Hartenstein, V. Neurogenesis in the primitive bilaterian NeochildiaI. Normal development and isolation of genes controlling neural fate. In prep.
Selected Publications
Tomancak, P., Berman, B.P., Beaton, A., Weiszmann, R., Kwan, E., Hartenstein V., Celniker, S.E. and Rubin, G.E.. 2007. Global analysis of patterns of gene expression during Drosophila Embryogenesis Genome Biol 8: R145- .
Pereanu, W., Spindler, S., Im, E., Buu, N. and Hartenstein., V. 2007. The emergence of patterned movement during late embryogenesis of Drosophila melanogaster Developmental Neurobiology : - .
Pereanu, W. and Hartenstein, V.. 2007. Neural lineages of the Drosophila brain: A 3D digital atlas of the pattern of lineage location and projection at the late larval stage J. Neurosci 26: 5534-5553 .
Mandal, L, Martinez-Agosto, J.A., Evans, C.J., Hartenstein, V. and Banerjee, U.. 2007. A Hedgehog- and Antennapedia-dependent niche maintains Drosophila haematopoietic precursors Nature 446: 320-324 .
Sprecher, S., Reichert, H., Hartenstein, V. and Ladurner, P.. 2007. Gene expression patterns in primary neuronal clusters of the Drosophila embryonic brain Gene Expr. Patterns 7: 584-595 .
Morris, J., Cardona, A., de Miguel-Bonet, M. and Hartenstein, V.. 2007. Neurogenesis in the basal platyhelminth Macrostomum lignano: Map and 3D digital mode of the juvenile brain Dev. Genes Evol 217: 569-584 .
Pfister, D., De Mulder, K.,Philipp, I., Kuales, G., Hrouda, M., Eichberger, P., Borgonie, G., Hartenstein, V. and Ladurner, P.. 2007. The exceptional stem cell system of Macrostomum lignano: Screening for gene expression and studying cell proliferation by hydroxyurea treatment and irradiation Front Zool 4: 9- .
Mandal, L., Martinez-Agosto, J.A., Evans, C.J., Hartenstein, V., Banerjee, U.. 2007. A Hedgehog- and Antennapedia-dependent niche maintains Drosophila haematopoietic precursors Nature 446: 320-324 .
Mandal, L., Dumstrei, K., and Hartenstein, V.. 2006. Role of FGFR signaling in the morphogenesis of Drosophila visceral musculature Dev. Dyn 231: 342-348 .
Hartenstein, V. and Mandal, L.. 2006. The blood/vascular system in a phylogenetic perspective Bioessays 28: 1203-1210 .