טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentBarak Hila
SubjectCharacterization of the Cellular and Molecular Mechanisms
that Govern the Formation of the Kidney
Morphogenetic Field
DepartmentDepartment of Biology
Supervisor Mr. Reshef Ram
Full Thesis textFull thesis text - English Version


Abstract

All vertebrate kidney tissue is derived from a strip of tissue called the intermediate mesoderm (IM). In the chick embryo, the kidney tissue is generated only from IM located posterior to the 6th somite axial level. This border is characterized by a specific gene expression in the IM, including Lim-1 and Pax-2. This observation suggests that at least two major types of cells arise along this axis, one anterior to the 6th somite level, which gives rise to a non-kidney tissue, and the other posterior to this axial level, which gives rise to a kidney tissue. In this study we asked whether specific anterior-posterior patterning information is conveyed by the movement of cells through the primitive streak at different time points that consequently affects the expression of kidney genes; or by the environment that these cells encounter during their migration to the IM. We propose a cellular mechanism to explain the formation of the anterior border of the kidney morphogenetic field. Two main themes emerged from these studies. The first was that kidney-inductive signals are present in the anterior non-kidney IM region and are secreted from the dorsal neural tube. The second theme suggests that IM cells lying anterior to the border do not express kidney genes due to a change in cell competence to respond to kidney inductive signals occurred during the migration of these cells from the primitive streak to their final destination in the anterior non-kidney IM. The expression pattern of several Hox genes was investigated during this study. Few of these Hox genes reveal expression pattern in the IM posterior to the 6th somite axial level that resembles the expression of pronephros markers in this tissue. Therefore, these Hox genes can serve as good candidates for mediating the formation of the anterior border of the kidney morphogenetic field. Administration of ectopic retinoic acid (RA) affects kidney gene expression and extends the kidney border anteriorly. Moreover, overexpression of RA catabolizing enzyme at early stages of pronephros specification shows that RA signalling plays an important role in early steps of pronephros patterning.  We present here a model in which changes in cell competence determine the formation of the anterior border of kidney gene expression and suggest possible molecular mechanisms that connect RA and Hox genes in determining and mediating the kidney morphogenetic field. We discuss here plausible evolutionary implications of this developmental mechanism.