Recherche - Observatoire océanologique de Banyuls sur mer
Laboratoire Arago

 Ming-Ji FANN ( departement of Life Sciences and Institute of Genome Sciences National Yang-Ming University, Taipei, Taiwan) présentera un séminaire le 4 Février 2011 ayant pour thème :

Control of vertebrate neurogenesis and skeletal formation

It is estimated that there are 765 predicted Ig superfamily (IgSF) members in the human genome and many are expressed in the developing embryos with unknown functions. We studied functions of one of IgSF members, protogenin (Prtg), and found its involvement in vertebrate neurogenesis and skeletal development. Prtg expresses in mouse embryos with a unique expression pattern. By immunofluorescence staining, a higher level of PRTG protein is detected in almost all cells of mouse embryos from E8.0 to E9.5, especially in the neural tube and somites. Expression of PRTG is barely detectable in mouse embryo after E10. Based on the expression pattern, we reasoned that PRTG may act as a gatekeeper for neurogenesis. Using assays based on neuronal differentiation of P19 cells and
chick embryos, we found that perturbation of PRTG activity or knockdown of endogenous Prtg increases neuronal numbers in P19 cells and chick embryos. We further identified ERdj3 as a PRTG extracellular interacting protein in a yeast two-hybrid screen. We demonstrated that ERdj3 is a secreted protein and a
bona fide PRTG ligand. Moreover, addition of ERdj3 in P19 differentiation assay inhibits neurogenesis, and blockage of ERdj3 facilitates neuronal formation in P19 and triggers apoptosis in chick embryo.

Together, these results suggest that expression of PRTG defines the primitive neural progenitors and activation of PRTG by ERdj3 initiates a pathway that suppresses premature neurogenesis in the developing nervous system. The Prtg knock-out mice were generated. Unexpectedly, there is no detectable malformation of the nervous system. However, defects in craniofacial and axial skeletons were detected. Our results reveal that the death of some neural crest cells leads to delayed formation of craniofacial bones and misexpression of Hox genes generates anterior transformation of axial skeletal bones. Thus, Prtg also plays critical roles in cranial bone formation and the identity of axial skeletons.

(This project was supported by National Science Council (NSC95-2320-B-010-059-MY2) and Ministry of Education, ROC.)