Axel Visel

Lawrence Berkeley National Laboratory
Genomics Division

MS84-171
1 Cyclotron Rd
Berkeley, CA 94720

Phone: 1-510-495-2301
Fax: 1-510-486-4229

e-mail: avisel at lbl dot gov

Axel




Research Interests

My research revolves around the fundamental question how the considerable complexity of the body and its organ systems can arise from a static genome whose sequence is identical in all cells.

A plethora of gene-centric studies, mainly in the domain of developmental biology, have highlighted the differential regulation of transcription as a most important mechanism that confers functional identity to cells. Precise control of gene regulation is a prerequisite for essentially all known pathways of organismal development. However, the identity of the regulatory regions that control gene expression in time and space has to date remained unknown for the vast majority of genes.

Comparative Vertebrate Genomics

The comparison of vertebrate genome sequences is a powerful tool to study the evolution of genomes at an unprecedented level of detail. In particular, comparative methods enable the identification of genome regions that are highly conserved between species, but do not encode proteins. Such non-coding sequence conservation may be due to a regulatory function of such elements. In fact, some types of conserved elements have been found to be highly enriched in developmental cis-regulatory activity. One focus of my current work in the laboratories of Eddy Rubin and Len Pennacchio at LBNL is the development and application of comparative genomic methods for identification of distant-acting enhancers in the human genome.

Mouse Transgenesis

Comparative genomics enables the identification of conserved non-coding genome elements that are likely to be developmental enhancers. In order to validate such enhancers and define the tissues to which they target gene expression during embryonic development, we use transgenic mouse methods. Experimental details, as well as transgenic results for several hundred human genome regions are available through the VISTA Enhancer Browser.




Publications

Visel A, Prabhakar S, Akiyama JA, Shoukry M, Lewis KD, Holt A, Plajzer-Frick I, Afzal V, Rubin EM, Pennacchio LA. Ultraconservation identifies a small subset of extremely constrained developmental enhancers. Nature Genet 2008, 40(2):158-60. PubMed
Moldrich RX, Laine J, Visel A, Beart PM, Laffaire J, Rossier J, Potier MC. Tmem50b (C21orf4), a candidate for Down syndrome neurophenotypes, encodes an intracellular membrane protein expressed in the rodent brain. Neuroscience 2008, 154(4):1255-1266. PubMed
Visel A, Carson J, Oldekamp J, Warnecke M, Jakubcakova V, Zhou X, Shaw CA, Alvarez-Bolado G, Eichele G. Regulatory Pathway Analysis by High-Throughput In Situ Hybridization. PLoS Genet 2007, 3(10):e234. PubMed Full Text Small PDF Large PDF
Ahituv N, Zhu Y, Visel A, Holt A, Afzal V, Pennacchio LA, Rubin EM. Deletion of ultraconserved elements yields viable mice. PLoS Biol 2007, 5(9):e234. PubMed Full Text Small PDF Large PDF
Visel A, Bristow J, Pennacchio LA. Enhancer identification through comparative genomics. Semin Cell Dev Biol 2007, 18(1):140-52. PubMed
Lein ES, Hawrylycz MJ, ..., Visel A, ..., Jones AR (108 authors). Genome-wide atlas of gene expression in the adult mouse brain. Nature 2007, 445(7124):168-76. PubMed
Visel A, Minovitsky S, Dubchak I, Pennacchio LA. VISTA Enhancer Browser--a database of tissue-specific human enhancers. Nucleic Acids Res 2007, 35:D88-92. PubMed Full Text Small PDF Large PDF
Pennacchio LA, Ahituv N, Moses AM, Prabhakar S, Nobrega MA, Shoukry M, Minovitsky S, Dubchak I, Holt A, Lewis KD, Plajzer-Frick I, Akiyama J, De Val S, Afzal V, Black BL, Couronne O, Eisen MB, Visel A, Rubin EM. In vivo enhancer analysis of human conserved non-coding sequences. Nature 2006, 444(7118):499-502. PubMed
Visel A, Alvarez-Bolado G, Thaller C, Eichele G. Comprehensive analysis of the expression patterns of the adenylate cyclase gene family in the developing and adult mouse brain. J Comp Neurol 2006, 496(5):684-97. PubMed
Yaylaoglu MB, Titmus A, Visel A, Alvarez-Bolado G, Thaller C, Eichele G. Comprehensive expression atlas of fibroblast growth factors and their receptors generated by a novel robotic in situ hybridization platform. Dev Dyn 2005, 234(2):371-86. PubMed Full Text PDF
Schumacher S, Laass K, Kant S, Shi Y, Visel A, Gruber AD, Kotlyarov A, Gaestel M. Scaffolding by ERK3 regulates MK5 in development. EMBO J 2004, 23(24):4770-9. PubMed Full Text PDF
Plas DT, Visel A, Gonzalez E, She WC, Crair MC. Adenylate Cyclase 1 dependent refinement of retinotopic maps in the mouse. Vision Res 2004, 44(28):3357-64. PubMed
Danilova N, Visel A, Willett CE, Steiner LA. Expression of the winged helix/forkhead gene, foxn4, during zebrafish development. Dev Brain Res 2004, 153(1):115-9. PubMed
Visel A, Thaller C, Eichele G. GenePaint.org: an atlas of gene expression patterns in the mouse embryo. Nucleic Acids Res 2004, 32:D552-6. PubMed Full Text PDF
Herzig U, Cadenas C, Sieckmann F, Sierralta W, Thaller C, Visel A, Eichele G. Development of high-throughput tools to unravel the complexity of gene expression patterns in the mammalian brain. Novartis Found Symp 2001, 239:129-46. PubMed




Links

Databases

VISTA Enhancer Browser - activity of conserved developmental enhancers in transgenic mouse embryos at e11.5
Genepaint.org - ISH-based expression atlas of the e14.5 mouse embryo
Allen Brain Atlas - Genome-wide ISH-based high-resolution expression atlas of the adult mouse brain

last edited Feb 2008