Ivan P. Moskowitz
| Years in MSTP | 1989-1998 |
| PhD | Biochemistry, 1996 |
| Mentor | Joel H. Rothman |
| Thesis |
Specification of Embryonic Blastomere Identity in the Nematode Caenorhabditis Elegans |
| Residency | Pathology, Childrens Hospital, Boston |
| Fellowship |
Genetics, Childrens Hospital, Boston |
| Investigative Research | Congenital heart disease |
| Current Position | Assistant professor, Committee on Genetics, genomics and system biology, University of Chicago |
Thesis Abstract
Most somatic cells in the nematode Caenorhabditis elegans arise from AB, the anterior blastomere of the two-cell embryo. The daughters of AB, ABa and ABp, adopt different fates as a result of their unique embryonic positions. We provide evidence that the cell surface receptor GLP-1 is required for a cellular interaction that makes ABp distinct from ABa.
By removing beta2, a neighboring cell, from early embryos, we show that the widespread differences between ABa and ABp arise from induction of the entire ABp fate by beta2. Lineage analyses of genetically and physically manipulated embryos further suggest that the identities of the AB great-granddaughters (ABp cells) are controlled by three regulatory inputs that act in combination.
These inputs are:
- Induction of the ABp-specific fate by Pb
- A previously described induction of particular ABp cells by MS, and
- A process that controls whether an ABp cell is an epidermal or a neuronal precursor in the absence of induction
When an ABp cell is caused to receive a new combination of these regulatory inputs, its lineage pattern is transformed to resemble the lineage of the wild-type ABp cell normally receiving that combination of inputs. Furthermore, we report that the GLP-1 and LIN-12 receptors, their ligand, LAG-2, and a downstream component, LAG-1, are required zygotically for two later inductions of AB descendants. We find that LAG-2 is expressed in the signaling cells and LIN-12 is expressed in cells receiving the inductions, consistent with their proposed roles as ligand and receptor, respectively.
Furthermore, we report that maternal GLP-1 activity is required:
- To repress early zygotic lag-2 expression and
- To activate zygotic lin-12 expression in the early embryo
The patterning of both receptor and ligand expression by maternal GLP-1 signaling establishes competence for the zygotic LNG-mediated cellular interactions and localizes these interactions to the appropriate cells. We propose that activation of maternal GLP-1 regulates zygotic lin-12 and lag-2 expression by a regulatory mechanism analogous to that described for the post-embryonic gonad.
Thesis Publications
Moskowitz IP, Rothman JH. lin-12 and glp-1 are required zygotically for early embryonic cellular interactions and are regulated by maternal GLP-1 signaling in Caenorhabditis elegans. Development 122:4105-4117, 1996.
Gendreau SB, Moskowitz IP, Terns RM, Rothman JH. The potential to differentiate epidermis is unequally distributed in the AB lineage during early embryonic development in C. elegans. Dev Biol 166:770-781, 1994.
Moskowitz IP, Gendreau SB, Rothman JH. Combinatorial specification of blastomere identity by glp-1-dependent cellular interactions in the nematode Caenorhabditis elegans. Development 120:3325-3338, 1994.