The ultimate goal of this work is to understand the molecular mechanisms controlling the assembly of the mammalian primitive streak and to elucidate the connection between this process and subsequent formation of mesodermal derivatives of the middle region of the streak. To investigate this, I will take a genetic approach. Only two mouse mutations have been identified to date that specifically affect the function of the middle region of the primitive streak, thus appearing to encode key players in a yet unknown pathway that governs primitive streak function. One of these, amn (amnionless), was previously characterized by the Lacy lab, which recently cloned the Amn gene. I will characterize and positionally clone the gene disrupted by the second of these mutations, noso (no somites). I will define noso?s function by analyzing expression of known molecular markers for primitive streak and mesoderm patterning in the noso mutant, in comparison with the amn mutant, to identify the major signaling pathway(s) perturbed by the two mutations. Using chimera analysis I will identify the tissues requiring wild-type noso function and demonstrate the degree of cellular autonomy of this function. Finally, I will clone the noso gene using genetic mapping in conjunction with a molecular complementation approach. The sequence and expression data on the noso gene, combined with the functional data, will provide a clear understanding of this gene?s involvement in primitive streak function and may suggest a link between the Amn and Noso proteins within a biochemical pathway.
| Lupu, Floria; Alves, Annabelle; Anderson, Kathryn et al. (2008) Nuclear pore composition regulates neural stem/progenitor cell differentiation in the mouse embryo. Dev Cell 14:831-42 |
