The Questions of Developmental Biology

Steps 7 and 8: Induction of mesenchymal stem cells by the ureteric bud, and the differentiation of
the nephron and growth of the ureteric bud
After the initial interactions create the first pretubular aggregates, the metanephrogenic
mesenchyme cells near the kidney border begin to proliferate to form stem cells. These stem cells
can interact with the ureteric bud branches to form new nephrons, or they can produce stromal
cells. The stromal cells migrate to the central portion of the kidney and produce factors (as yet
unknown) that (1) enable the continued growth of the ureteric bud and (2) stimulate the
differentiation of the nephron into the convoluted renal tubules, Henle's loop, the glomerulus, and
the juxtaglomerular apparatus.
The transcription factor BF-2 is synthesized in these stromal cells. When it is knocked
out in mouse embryos, the resulting kidney lacks a branched ureteric tree (it branches only three
or four times instead of the normal seven or eight, resulting in an 8- to 16-fold reduction in the
number of branches), and the aggregates do not differentiate into nephrons (Hatini et al. 1996). So
it appears that the factors necessary for ureteric epithelial growth and nephron differentiation are
synthesized by the stromal cells and are regulated by transcription factor BF-2.
The stromal cells have been found to secrete FGF7, a growth factor whose receptor is
found on the ureteric bud. FGF7 is seen to be critical for maintaining ureteric epithelial growth,
and consequently, ensuring an appropriate number of nephrons in the kidney (Qiao et al. 1999).
In the developing kidney, we see an epitome of the reciprocal interactions needed to form
an organ. We also see that we have only begun to understand how organs form.
*The mesenchymal to epithelial transition appears to be mediated by the expression of Pax2 in the newly induced
mesenchyme cells. When antisense RNA to Pax2 prevents the translation of the Pax2 mRNA that is transcribed as a
response to induction, the mesenchyme cells of cultured kidney rudiments fail to condense (Rothenpieler and Dressler
1993
Snapshot Summary: Paraxial and Intermediate Mesoderm
1. The paraxial mesoderm forms blocks of tissue called somites. Somites give rise to three major
divisions: the dermatome, the myotome, and the sclerotome.
2. The dermatome of the somite forms the back dermis. The sclerotome of the somite forms the
vertebral cartilage. In thoracic vertebrae, the sclerotome cells also form the proximal portions of
the ribs.
3. The epaxial myotome forms the back musculature. The hypaxial myotome forms the muscles
of the body wall, limb, and tongue.
4. Somites are formed from the segmental plate (unsegmented mesoderm) by a combination of
proteins. The Hairy protein, a transcription factor, appears to specify the somite boundaries.
Notch and Eph receptor systems may be involved in the separation of the somites from the
unsegmented paraxial mesoderm. N-cadherin and fibronectin appear to be important in causing
these cells to become epithelial.
5. The somite regions are specified by paracrine factors secreted by neighboring tissue. The
sclerotome is specified to a large degree by the Sonic hedgehog protein, secreted by the
notochord and floor plate cells. The dermatome is specified by neurotrophin-3, secreted by the
roof plate cells of the neural tube.