Biomedical Engineering Reference
In-Depth Information
A/P patterning regulates cell adhesion and junctional remodeling that leads
to changes in cell geometry, resulting in the formation of multicellular
rosette structures. The rosettes resolve themselves along the A/P axis,
resulting in tissue thinning and elongation, a process that can broadly be
described as convergent extension (CE) (
Blankenship et al., 2006
).
A distinct set of factors that are localized to the adherens junctions such as
the Par3, Scribbled, and nonmuscle myosin homologs are required for CE
during Drosophila germband extension (
Blankenship et al., 2006; Djiane,
Yogev, & Mlodzik, 2005; Gray et al., 2011; Montcouquiol et al., 2003;
Zallen & Blankenship, 2008
). Interestingly, although these factors show
planar-polarized expression within cells similar to what is observed for the
core PCP proteins, mutations in Fz and Dsh do not affect these
morphogenetic movements. These studies emphasize that not all PCP is
equivalent. Multiple independent pathways most likely regulate PCP in
tissue-specific manners. Therefore, defects in seemingly unrelated cellular
processes can lead to similar effects on the entire tissue. This is an important
point, especially when one begins to consider all the pathologies that have
been attributed to PCP defects in the kidney.
3. KIDNEY DEVELOPMENT
The formation of themammalian permanent kidney, or metanephros, is
initiatedwhen an epithelial bud (theuretericbud) forms fromtheWolffianduct
and invades the surrounding mesenchyme (known as the metanephric mesen-
chyme,MM). TheMMconsists of at least two cell types. Cells that lie closest to
and surround the ureteric bud are collectively referred to as the cap mesen-
chyme. A second population of cells lies distal to the ureteric bud and adjacent
to the capmesenchyme and is referred to as the cortical interstitium. Following
its invasion into the mesenchyme, the ureteric bud epithelium undergoes
branching morphogenesis forming a highly complex, tree-like system of tubes
that make up the renal collecting duct system of the mature kidney.
The capmesenchyme contains a self-renewing, multipotent progenitor cell
population that proliferates with the branching ureteric buds so that each new
bud tip is covered by cap mesenchyme (
Boyle et al., 2008; Kobayashi et al.,
2008
). After each round of branching, a subpopulation of the cap
mesenchyme will undergo a mesenchymal-to-epithelial transition just below
the ureteric bud tips forming a pretubular aggregate and then a primitive
epithelial structure known as the renal vesicle. The renal vesicle will undergo
extensive morphogenesis to form the nonvascular portion of the nephron.
