Home Faculty and Research Faculty by Name Sharon Amacher

Sharon Amacher

Associate Professor of Genetics, Genomics and Development

Lab Homepage: http://mcb.berkeley.edu/labs/amacher/

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Research Interests

We are interested in how cells become sequentially determined to more precisely defined fates during vertebrate embryonic development, and how this process depends upon cell position and upon interactions among neighboring cells. To address these questions, we use genetics, molecular biology, and embryology to investigate mesodermal patterning and segmentation in the zebrafish embryo.

Current Projects

Mesodermal patterning. The embryonic mesoderm is specified during gastrulation, with dorsal mesoderm becoming notochord, lateral (paraxial) mesoderm forming muscle, and ventral mesoderm becoming blood. Although fate mapping experiments show that mesodermal cells become restricted to specific fates during early gastrulation, transplantation experiments show that fates are not fixed until later. Thus, local cell-cell interactions are critical for reinforcing cell fate decisions. We are characterizing the molecular and cellular events involved in patterning the gastrula mesoderm. spadetail (spt), a gene encoding a T-box transcription factor, is required for proper gastrulation movements and fate specification of paraxial mesodermal (somitic) cells, whereas no tail (ntl), a gene encoding another T-box family member, is critical for development of the axial (notochordal) mesoderm. Together, the two T-box genes are important for the development of all mesodermal types. To understand how spt and ntl mediate mesodermal cell fate decisions, we have identified putative target genes using zebrafish microarrays, and are currently investigating the expression and function of putative targets, as well as identifying and characterizing the regulatory regions that control their T-box-regulated expression.

Mesodermal segmentation. Following gastrulation, the paraxial mesoderm becomes visibly segmented into a reiterated series of tissue blocks called somites. Somitogenesis involves cell-cell interactions that convert a field of identical cells into a set of individual compartments, each of which is patterned along the anterior to posterior axis. spt acts near the top of the pathway to get cells to the right place at the right time; we would like to identify other segmentation genes.

To assemble a genetic pathway regulating segmentation, we are searching for additional genes using a variety of approaches. We are performing a genetic screen to identify mutations that disrupt segmental gene expression of her1, a homolog of the Drosophila pair-rule gene hairy. We have found several mutants and are characterizing their phenotypes. In addition, we are mapping each mutation as a first step toward molecular identification of the genes. To identify other genes in the pathway, we are using DNA microarrays to find genes differentially expressed in wild-type and mutant embryos. We find other interesting candidates based upon their expression patterns and examine how they might function in the pathway using molecular epistasis and loss-of-function approaches. Finally, because entire pathways are often conserved, we are also isolating homologs of segmentation genes identified in other organisms. These homologs will be potential candidates for genes identified by mutation, as well as tools in our phenotypic analyses.

Cellular interactions during somitogenesis. We anticipate that close range cellular interactions are important for somite formation and differentiation. We use a variety of imaging techniques to examine somitic cell behaviors  in the live zebrafish embryo. To understand mutant phenotypes, and thus gene function, at the level of single cells, we are using time-lapse microscopy of wild-type and mutant embryos to observe cell-cell contacts and interactions occurring in paraxial mesoderm before, during, and after somites form. We have discovered that a small population of first-differentiating muscle cells induces the morphogenesis of their neighbors as they migrate through the somite to their final position; currently, we are pursuing the molecular nature of the trigger.

Selected Publications

Interactions between muscle fibers and segment boundaries in zebrafish. [C. A. Henry, I. M. McNulty, W. A. Durst, S. E. Munchel, and S. L. Amacher (2005) Dev Biol, 287, 346-350]

tortuga refines Notch pathway gene expression in the zebrafish presomitic mesoderm at the post-transcriptional level. [K. K. Dill and S. L. Amacher (2005) Dev Biol, 287, 225-236]

Zebrafish slow muscle cell migration induces a wave of fast muscle morphogenesis. [C. A. Henry and S. L. Amacher (2004) Dev Cell, 7, 917-923]

Developmentally restricted actin regulatory molecules control morphogenetic cell movements in the zebrafish gastrula. [D. F. Daggett, C. A. Boyd, P. Gautier, R. J. Bryson-Richardson, C. Thisse, B. Thisse, S. L. Amacher, and P. D. Currie (2004) Curr Biol, 14, 1632-1638]

Two linked hairy/enhancer-of-split-related zebrafish genes, her1 and her7, function together to refine alternating somite boundaries. [C. A. Henry, M. K. Urban, K. K. Dill, J. P. Merlie, M. F. Page, C. B. Kimmel, and S. L. Amacher (2002) Development, 129, 3693-3704]

The zebrafish T-box genes no tail and spadetail are required for development of trunk and tail mesoderm and medial floor plate. [S. L. Amacher, B. D. Draper, B. R. Summers, and C. B. Kimmel (2002) Development, 129, 3311-3323]

Transcriptional regulation during zebrafish embryogenesis. [S. L. Amacher (1999) Curr Op Genet Dev 9, 548-552]

Molecular identification of spadetail: regulation of zebrafish trunk and tail mesoderm formation by T-box genes. [K. J. Griffin, S. L. Amacher, C. B. Kimmel, and D. Kimelman (1998) Development 125, 3379-3388]

Promoting notochord fate and repressing muscle development in zebrafish axial mesoderm. [S. L. Amacher and C. B. Kimmel (1998) Development 125, 1397-1406]

Last Updated 2006-09-19