Identification of novel genes potentially involved in hindbrain segmentation

Lines connect the coordinator with its partners. CORDIS does not always give exact coordinates for projects before 2014. These points are placed at city or country level.

Project objective

Research objectives and content This project is designed to identify novel mouse genes expressed in a segment-specific manner in developing hindbrain, without any presupposition on their identity. We will take advantage of the existence of mice carrying a null mutation in the gene Krox-20, which results in an elimination of rhombomeres number 3 and 5. We will apply the procedure of Differential RNA Display to this very clean genetic system, which should allow the identification of genes specifically expressed in the segments affected by the mutation. In practice, we have already performed preliminary experiments which have led to the cloning of several sequences which are amplified with wild type RNA but not with mutant RNA. We will continue this analysis to accumulate additional candidate clones. These will then be used in whole mount in situ hybridisation experiments to establish whether their expression is indeed restricted to rhombomeres 3 or 5 during hindbrain development. The positive clones will be sequenced and, if they correspond to novel genes, they will be used to isolate complete cDNAs in order to initiate their functional analysis. Particular efforts will be put on genes encoding adhesion molecules, if such genes are revelad by this work. Training content (objective, benefit and expected impact) The morphogenesis of the vertebrate hindbrain is subjected to a segmentation process which sets essential aspects of its neuronal architecture. To have access to the molecular mechanisms governing this phenomenon, it is essential to identify the genes which play a role in its control. It is expected that many of these will be expressed in a segment-specific manner. Indeed a few genes with such an expression pattern have been identified, either by accident or by systematic search among known gene families. In this project, we plan to identify novel genes expressed specifically in segments 3 or 5 and to initiate their functional analysis. If successful, this work should open the door to major extension of our knowledge of the genetic control of hindbrain segmentation.

Original text from CORDIS.

Participants

• INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE · PARISCoordinatorFrance
• Not availableCity levelSpain

Links

• View on CORDIS