Intermediate and lateral plate mesoderm

Kidney develops through interactions of mesenchyme and epithelium

Both the mesenchyme and epithelium are derived from the intermediate mesoderm

mesenchyme will form

renal tubules and Bowman’s capsules

epithelium will form

collecting ducts of kidney

Epithelium starts as

uteric bud, which contacts mesenchyme

Signaling for mesenchyme

mesenchyme cells produce GDNF and receptors for GDNF are present on the uteric bud

GDNF produced by mesenchyme

promotes division of these cells and is necessary for branching, this would lead to a particular branching pattern - new bifurcations, but just at the tips

Equal growth of branching

Make circle

Uteric bud signals to mesenchyme

Produces FGFs and BMP7 - when those are present, mesenchyme cells don’t undergo apoptosis, but proliferate

Why is uteric bud signals helpful for development of nephron?

Ensure mesenchyme cells are able to connect to bud

Wnt proteins from uteric bud

Induces mesenchyme cells to form an epithelium and produce E-cadherin

Lateral plate mesoderm produces

Extraembryonic membranes, lining of the body cavities, circulatory system - blood vessels and blood cellsVas

Vasculogenesis

Initial formation of blood vessels

cells on inside of aggregations

produce blood cells

Cells on outside of aggregations

become angioblasts - will produce the blood vessels

More notch signaling

Cells to become blood cells

Less notch signaling

blood vessels

Angioblasts proliferate

form endothelial cells → form tubes producing anetwork of capillaries

3 molecules involves invasculogenesis

FGF2 → production of blood island cells from lateral plate mesoderm

VEGF-A → formation of tubes by endothelial cells

angioprotein-1 → endothelial tubes to recruit precursors of smooth muscle cells to surround the blood vessel

remodeling capillary networks

• VEGF-A causes breakdwon of extracellular matrix at same locations on capillaries

• Endothelial cells proliferate and form new blood vessels

  • VEGF also promotes the endothelial cell proliferation

Lack of oxygen

cells express VEGF → gets more blood vessels to bring it oxygen

Tip cells

cells taht divide and make a new blood vessel in response to VEGF by making delta to make new capillary. This activates notch on cells next to them, those don’t respond to VEGF-A

Murray’s law

describes the arrangement that requires the least energy to move liquid through blood vessels

• the cross sections of the small branches will add up to more than the cross sections of the large branch they come off of, keep flow from speeding up as the fluid goes into the small branches where resistance to flow is high

Flow was faster than optimal

Shear stress would be high, triggers cells to proliferate and increase blood vessel diameter, reduce shear stress.

Shear stress

Activates both integrin and VEGF-A receptor in endothelial cells, the receptor is activated without the presence of its ligand to divide further to adjust