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Somatic vs Splanchnic Mesoderm
Somatic mesoderm + ectoderm form the body wall; splanchnic mesoderm + endoderm form gut-associated tissues and the heart
Somatopleure
Tissue layer of somatic mesoderm + ectoderm forming limbs and body wall
Splanchnopleure
Tissue layer of splanchnic mesoderm + endoderm forming heart tube surfaces and gut
Coelom Formation
Fusion of left and right coeloms to form pleural, pericardial, and peritoneal cavities
Cardiogenic Mesoderm Location
Located in splanchnic mesoderm of LPM; forms heart fields
Single Progenitor for Cardiovascular System
One precursor population produces cardiomyocytes, endocardium, valves, conduction system, and blood cells
Anterior Endoderm Functions
Specifies cardiogenic mesoderm and guides bilateral heart fields to midline
Experiment: Removing Endoderm
Prevents heart field migration and produces cardia bifida (two hearts)
Cardia Bifida Cause
Loss of fibronectin-guided migration cues prevents fusion of heart fields
Primary Heart Field Fate
Forms the left ventricle
Secondary Heart Field Fate
Forms right ventricle, atria, and outflow tract
Heart Looping Purpose
Positions atria above ventricles for correct adult heart orientation
Hemangioblasts
Progenitor cells that generate blood vessels and blood cells
Vasculogenesis vs Angiogenesis
Vasculogenesis creates vessels de novo; angiogenesis creates vessels from existing ones
VEGF Function
Promotes endothelial differentiation, tube formation, and vascular sprouting
Hypothetical: Block VEGF Early
Embryo fails to form vessel network and dies
Hypothetical: Overexpress VEGF in One Limb
Produces a hypervascular limb with excess sprouting
Paraxial Mesoderm Specifies IM
Removing paraxial mesoderm prevents intermediate mesoderm formation
Nephric Duct Function
Induces pronephros, mesonephros, and ureteric bud formation
Pronephros Fate
First kidney; degenerates in mammals but functional in fish and amphibians
Mesonephros Fate
Temporary kidney in mammals; forms parts of male reproductive system
Metanephros (Adult Kidney)
Forms via reciprocal signaling between metanephric mesenchyme and ureteric bud
Reciprocal Induction Logic
Mesenchyme induces ureteric bud via GDNF; bud prevents mesenchyme apoptosis via FGF and BMP
Experimental: Remove GDNF
No ureteric bud forms and kidneys fail to develop
Experimental: Overexpress GDNF
Multiple ureteric buds form and kidneys may be duplicated
Wnt Exposure Timing Rule
Early/short Wnt makes ureteric epithelium; late/long Wnt makes nephron mesenchyme
Branching Morphogenesis Cause
Driven by GDNF-RET signaling causing iterative branching of ureteric bud
Mesenchyme-to-Epithelium Transition in Kidney
Nephron precursors undergo MET to form renal tubules and Bowman’s capsule
Nephron vs Collecting Duct Origins
Nephron arises from mesenchyme; collecting duct arises from ureteric bud
Wnt9b Role
Required for converting mesenchyme to tubular epithelium; mutants lack kidneys
Hypothetical: Inhibit RET Receptor
Ureteric bud cannot respond to GDNF, leading to kidney agenesis
Bladder Development Note
Nephric duct connects to cloaca; ureteric bud migrates separately into bladder
Somites
Repeating segmented blocks of paraxial mesoderm forming vertebrae, ribs, dermis, and muscle
Somite Compartments
Sclerotome forms bone; dermamyotome forms muscle and dermis
Somitogenesis Direction
Somites form anterior to posterior via MET
Segmentation Clock Discovery
Hairy1 oscillations in presomitic mesoderm reveal timing mechanism for somite formation
Hairy1 Oscillatory Pattern
Begins posterior, moves anterior, stabilizes at new somite boundary
Notch Pathway Role in Somites
NICD induces hairy and Lfng, which then suppress Notch to create oscillations
Determination Front
Region where low FGF and high retinoic acid allow somite formation
Clock-and-Wavefront Model
Clock defines when somites form; wavefront defines where they form
Experiment: Increase FGF Gradient
Wavefront shifts posterior, producing fewer large somites
Experiment: Decrease FGF
Somites form prematurely and produce many small somites
Mesp Function
Turns on MET to establish a new somite at the determination front
Species Differences in Segmentation Clock
Zebrafish 30 min; chick 90 min; mouse 120 min; human 5 hours
Notch Pathway Mutants
Mutations in clock genes produce fused or disorganized vertebrae
Human Congenital Scoliosis Cause
Segmentation clock defects result in irregular somite boundaries
Hypothetical: Inhibit Notch Oscillation
Somite periodicity is lost, causing fused or malformed vertebrae
Limb patterning axes
Limbs are patterned along anterior–posterior, dorsal–ventral, and proximal–distal axes.
Proximal–distal limb regions
Stylopod (upper limb), zeugopod (forearm), autopod (hand/foot).
Source of limb muscles
Limb muscles come from paraxial mesoderm (somites).
Source of limb bones
Limb bones come from lateral plate mesoderm.
Limb bud definition
Early outgrowth of mesoderm covered by ectoderm that becomes the limb.
Proximal–distal signaling
RA from the flank specifies proximal fates; FGFs/Wnts from the AER specify distal fates.
Role of retinoic acid
Promotes proximal limb identity like stylopod formation.
Role of FGFs/Wnts
Promote distal limb identity and drive elongation.
Hox genes function
Pattern the limb skeleton and define stylopod, zeugopod, and autopod identities.
Hox11 mutant phenotype
Missing zeugopod bones (radius, ulna, tibia, fibula).
Hox13 mutant phenotype
Autopod defects: malformed digits, fusions.
Apical Ectodermal Ridge (AER)
Distal ectodermal thickening that signals for limb outgrowth.
AER removal result
Limb development stops; distal structures fail to form.
Extra AER result
Causes duplicated limb structures.
AER signals
Secretes FGFs (especially Fgf8) to maintain limb growth.
FGF bead rescue
An FGF-soaked bead can replace the AER and restore limb development.
Progress zone definition
Mesenchyme beneath the AER kept proliferative and undifferentiated.
Arm vs. leg mesenchyme swap
Mesenchyme determines limb type; arm mesenchyme makes arm, leg mesenchyme makes leg.
Non-limb mesenchyme swap
Causes AER regression and stops limb development.
ZPA definition
Posterior limb region controlling anterior–posterior patterning.
ZPA transplant result
Causes mirror-image digit duplication.
Shh location
Expressed in posterior limb mesenchyme, same region as the ZPA.
Shh gain-of-function
Anterior Shh causes duplicated digits like a ZPA transplant.
Digit identity + Shh
No Shh = digit 1; Shh concentration = digits 2–3; Shh duration = digits 4–5.
Dorsal vs. ventral limb
Dorsal = nails/knuckles; ventral = palm.
DV patterning genes
Wnt7a and Lmx1b specify dorsal identity; BMP/En1 specify ventral.
Lmx1b mutant phenotype
Dorsal limb becomes ventralized.
Human LMX1B condition
Nail-patella syndrome (nail/patella defects).
Interdigital webbing removal
Webbing is removed through apoptosis in interdigital tissue.
Species differences in webbing
Ducks and bats keep webbing because apoptosis isn’t induced.
BMP role in webbing
BMP triggers apoptosis in interdigital cells.
Gremlin function
Gremlin inhibits BMP, preventing apoptosis.
Gremlin bead experiment
Adding Gremlin reduces apoptosis and makes chick digits more duck-like.