BIOL 3010 Lecture Notes - Lecture 18: Bone Morphogenetic Protein 7, Bone Morphogenetic Protein 4, Proteoglycan

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29 Jan 2013
Outline of Lecture 18
Kidney Development
I. The kidney is designed to filter the blood
A) Functions: regulate body fluid osmolarity and volume; electrolyte and acid-
base balance; produce EPO
B) Gross anatomy (p.1 figure): ureter, hilus, medulla, cortex, nephron
C) Nephron structures (p.2 figure): Bowman’s capsule, glomerulus, renal
corpuscle, podocytes, basement membrane; ascending and descending limbs,
collecting duct
II. Kidney development
- The intermediate mesoderm gives rise to the pronephros, mesonephros, and
metanephros, which develop in that order and each elongate caudally
1) Pronephros: mesenchymal cells from the 10th somite migrate and proliferate to
form the pronephric duct, which degenerates and has no mammalian function
2) Mesonephros: forms in the nephrogenic cord; meson. tubules connected by
meson. duct, which leads to urogenital sinus; becomes part of male reproductive
3) Metanephros: develops into adult kidney
- ureteric bud from the mesonephric duct invades metanephric mesenchyme and
induces nephron formation
- mesenchymal condenses to form blastema, which develops into a primitive
nephron in a process that involves reciprocal inductions
- ureteric branching gives rise to the whole complement of nephrons
- blood vessels follow ureteric bud, which allows proper contact at each
- kidney shifts from pelvic region to abdominal region and contacts
adrenal gland
III. Genes involved in kidney induction
A) Initiation of duct formation
- Lim1: txn factor expr by intermediate mesoderm required for duct
- Pax2 and Sim1: other txn factors that are also involved
- BMP4 (from ectoderm), RA and activin (somite): specify nephric field
B) GDNF/Ret induces ureteric bud outgrowth, an early step in nephron
- GDNF is a secreted molecule expressed by intermediate mesoderm
- Spatial expr of GDNF is determined by WT-1 and Pax2 (+) and FoxC1 and
FoxC2 (-); also, BMP4 limits Ret signaling to caudal region
- GDNF binds Ret receptor on the ureteric bud, which activates MAPK and PI3K
pathways, which leads to ureteric bud outgrowth and mesenchyme
C) Ureteric bud branching involves some of the same factors
- Emx-2: a txn factor that regulates molecules that signal for branching
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