טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentPreger Ella
SubjectCreating Borders during Embryonic Development: Molecular
Mechanisms that Govern the Formation of the
Anterior Border of the Kidney
Morphogenetic Field
DepartmentDepartment of Biology
Supervisor Mr. Reshef Ram
Full Thesis textFull thesis text - English Version


Abstract

Organs and structures arise at particular locations along the anterior-posterior embryonic axis. The kidney is an example of an organ that develops in a specific position along this axis. All vertebrate kidney tissues are derived from a strip of tissue called the intermediate mesoderm (IM), which is located between the somites and the lateral plate mesoderm of the developing embryo. The kidney tissue in chick embryos is generated only from IM located posterior to the 6th somite axial level . This 6th somite border also marks the border between cranial and trunk segments and is characterized by a specific profile of gene expression in the IM, including Lim-1 and Pax-2. IM cells lying anterior to this level do not express kidney genes due to changes in cell competence in responding to kidney inductive signals present along the entire axis. The loss of competence occurs during gastrulation stages when these cells migrate from the primitive streak to their final destination in the anterior non-kidney IM .

In the present study we aim at understanding the molecular mechanisms that govern this loss of competence and consequently the formation of the anterior border of the kidney morphogenetic field. First, we have identified the dorsal neural tube as the potential kidney-inductive tissue and have shown that Activin, a secreted morphogene, is necessary but insufficient for the induction of Lim-1 and the establishment of the kidney field. In addition, Activin and the bone morphogenic protein (BMP) signaling cascades were shown to be activated along the entire axis including anterior non-kidney IM, suggesting that cell competence to respond to these signals involves downstream or other components. Therefore, we have investigated a potential role for Hox genes in this process and demonstrated that paralogous group four genes share the same anterior border of the kidney gene makers within the IM. Ectopic expression of Hoxb4 in anterior-non kidney IM either by retinoic acid (RA) administration or by plasmid mediated over-expression results in kidney gene expression in the anterior IM. However, the anterior expansion of Lim-1 expression was restrained when Hoxb4 was co-expressed together with a truncated form of the Activin receptor. We suggest a model according to which the competence of cells in the IM to respond to TGF-β signaling and express kidney genes is driven by RA and mediated by Hoxb4.