טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentHanina Gili
SubjectRegulation of Hoxb4 Expression during the Formation of the
Kidney Morphogenetic Field
DepartmentDepartment of Biology
Supervisors Professor Dina Ron
Mr. Reshef Ram
Full Thesis textFull thesis text - English Version


Abstract

During embryonic development, organs are formed in specific positions along the anterior-posterior axis of the developing body. The kidney is an example of such an organ. In vertebrates, kidney tissues are derived from a narrow tissue called the intermediate mesoderm (IM). In chick embryos, the kidney tissue is generated only from IM located posterior to the 6th somite axial level and is characterized by a specific profile of gene expression, including Lim1 and Pax2. This observation suggests two cells populations of the IM along this axis, one in the IM anterior to the 6th somite level, which gives rise to a non-kidney tissue, and the other in the IM posterior to this axial level, which gives rise to a kidney tissue. Recent studies in our lab have shown that kidney inductive signals are present along the entire axis, and that cells that lay in anterior IM lose their competence to respond to these signals during their migration from the primitive streak to their final destination in the anterior non-kidney IM . Additionally, the competence of prospective IM cells to respond to kidney inductive signals has been shown to be conferred by the expression of Hoxb4.

In the present study we aim at combining the cellular and molecular knowledge that have been gathered regarding the kidney morphogenetic field and to investigate the regulation of Hoxb4 in IM cells. We show that the expression of Hoxb4 is evident along the entire length of the primitive streak from relatively early stages. However, while it is maintained in posterior IM cells, it is lost from anterior IM cells that migrate out of the primitive streak earlier. In order to discover the factors that govern the creation of this border between the two IM cell populations, we analyzed the expression patterns of three retinoic acid (RA) synthesizing genes: Stra6, Rdh10 and Raldh2, hypothesizing a role for RA in the regulation of the differential expression of Hoxb4. Based on the expression patterns of these genes we built a model that represents the predicted distribution of RA in mesodermal tissues. According to this model RA cannot be responsible for the expression of Hoxb4 in early stages in the primitive streak. Rather, we suggest a mechanism in which RA play a role in maintaining Hoxb4 expression in the mesoderm at later stages, as its expected distribution is divided into anterior and posterior regions, concordant with the kidney morphogenetic field.