Contrasting expression patterns of three members of the myc family of protooncogenes in the developing and adult mouse kidney.

Abstract

Abstract. The myc family of protooncogenes encode similar but distinct nuclear proteins. Since N-myc, e-myc, and L-myc have been found to be expressed in the newborn kidney, we studied their expression during murine kidney development. By organ culture studies and in situ hybridization of tissue sections, we found that each of the three members of the myc gene family shows a remarkably distinct expression pattern during kidney development. It is known that mesenchymal stem cells of the embryonic kidney convert into epithelium if properly induced. We demonstrate that N-myc expression increases during the first 24 h of in vitro culture as an early response to induction. Moreover, the upregulation was transient and expression levels were already low during the first stages of overt epithelial cell polarization. In contrast, neither c-myc nor L-myc were upregulated by induction of epithelial differentiation, e-myc was expressed in the uninduced mesenchyme but subsequently became restricted to the newly formed epithelium and was not expressed in the surrounding loose mesenchyme. At onset of terminal differentiation c-myc expression was turned off also from the epithelial tubules. We conelude that N-myc is a marker for induction and early epithelial differentiation states. That the undifferentiated mesenehyme, unlike stromal cells of later developmental stages, express c-myc demonstrates that the undifferentiated mesenchymal stem cells are distinct from the stromal cells. The most astonishing finding, however, was the high level of L-myc mRNA in the ureter, ureter-derived renal pelvis, papilla, and collecting duets. In the ureter, expression increased, rather than decreased, with advancing maturation and was highest in adult tissue. Our results suggest that each of the three members of the myc gene family are involved in quite disparate differentiation processes, even within one tissue.

Upregulation of c-MYC in WT1-mutant tumors: assessment of WT1 putative transcriptional targets using cDNA microarray expression profiling of genetically defined Wilms' tumors

“…In the mouse embryonic kidney, c-MYC is expressed in both early (uninduced mesenchyme and also induced and condensing mesenchyme) and later (tubule elongation) differentiation stages, and its expression is observed in mitotically active cells in these structures. No c-MYC expression is observed in terminally differentiated structures of the kidney (Mugrauer and Ekblom, 1991), consistent with c-MYC expression being correlated with cell proliferation. Unlike c-MYC, WT1 is (Nisen et al, 1986).…”

RB and c-Myc Activate Expression of the E-Cadherin Gene in Epithelial Cells through Interaction with Transcription Factor AP-2

“…For example, RB expression is high in the nervous system and in various epithelial cells, such as kidney collecting tubules and skin, where it is confined in the more differentiated layer; these are also the tissues where AP-2 expression is high (34). Moreover, Myc expression is also found during tubulogenesis in kidney (38,45). Thus, all three proteins may cooperate during the developmental differentiation of particular epithelial tissues.…”

c-Myc Signalling in the Genetic Mechanism of Polycystic Kidney Disease

“…Normally, endogenous c-Myc is expressed early in uninduced renal mesenchyme, but also in the comma-shaped bodies, S-shaped bodies, and elongating tubules from e11.5-16.5. Upon renal maturation, cMyc expression decreases to undetectable levels postnatally in differentiated renal tubular epithelium (50,51). In comparison to c-Myc, N-Myc expression is even more transient with high levels upon renal mesenchyme induction, and is undetectable once the transition to epithelium is completed, whereas L-myc expression is confined to epithelium of the ureteric bud derivatives, in particular the collecting ducts (50).…”