Exam 3: Neurulation, somites, muscle and bone, gut and lungs, facial, eyes, (Teratrogens, Infections, and Microchimerism)

What is neurulation?

Process that forms the neural tube (future brain and spinal cord)

When does neurulation occur in humans?

Around the 3rd week

What tissue is transformed during neurulation?

Ectoderm → neural tube

Is neurulation similar across species?

Yes, it is similar in all vertebrates

What is primary neurulation?

Folding of neural plate to form neural tube

What is secondary neurulation?

Formation of neural tube from a solid medullary cord that later cavitates

When do the two neural tube regions connect?

Around week 6

What are the 4 main steps of neurulation?

Neural plate formation

Shaping

Bending

Closure

What structure signals ectoderm to become neural tissue?

Notochordal process

What is Hensen's node?

Organizer region that helps initiate neural development

What process lengthens the neural plate?

Convergent extension

What happens to ectoderm cells?

Become elongated (columnar) and form neural plate

What happens during shaping?

Plate narrows, thickens, and lengthens

What forms at the edges of the neural plate?

Neural folds

What is the neural groove?

Depression between folds

What signaling molecule drives bending?

Sonic hedgehog (Shh)

What adhesion change occurs during closure?

E-cadherin → N-cadherin and N-CAM

What happens to the neural tube after closure?

Separates from surface ectoderm

What cells form at the fusion point?

Neural crest cells

What signaling levels specify neural crest cells?

Intermediate BMP, high Wnt

What process allows neural crest migration?

EMT (epithelial-to-mesenchymal transition)

What happens to adhesion molecules?

Decrease (CAMs and tight junctions)

What is Waardenburg syndrome?

Disorder with pigmentation defects and hearing loss

What causes Hirschsprung's disease?

Lack of neural crest cells in gut → no innervation

What are symptoms of Hirschsprung's?

Bowel issues, swollen abdomen, possible megacolon

How does fetal alcohol syndrome affect development?

Disrupts neural crest migration → facial and brain defects

What structure forms first in secondary neurulation?

Medullary cord

How does the medullary cord become a tube?

cavitation

Which end closes first?

Head (cranial region)

What remains active in the tail region?

Primitive streak and node

How common are NTDs?

1-4 per 2000 births

What determines severity?

Location of failed closure

How much can folic acid reduce NTD risk?

About 50%

Why is folic acid important?

DNA replication and methylation

What gene is linked to folate metabolism defects?

MTHFR

What drug can increase NTD risk?

Valproic acid

Spina bifida occulta?

Mild, hidden, often no symptoms

Closed spinal dysraphism?

Tissue abnormalities → weakness, bowel/bladder issues

Meningocele?

CSF-filled sac, mild symptoms

Myelomeningocele?

Severe; nerves exposed

What causes anencephaly?

Failure of cranial neural tube closure

What happens to brain tissue?

Degenerates due to exposure

Outcome of anencephaly and exencephaly?

Usually lethal shortly after birth

What is craniorachischisis?

Entire neural tube (brain + spinal cord) remains open

Is craniorachischisis survivable?

No, not compatible with life

Key processes in neurulation?

Neural plate formation, folding, closure, neural crest migration, neural tube defects if disrupted

What are somites?

Paired blocks of mesoderm that form along the anterior-posterior axis and give rise to vertebrae, muscles, and dermis.

Where do somites originate?

Paraxial mesoderm.

What are the three compartments of a somite?

Sclerotome, myotome, dermatome.

What does the sclerotome form?

Vertebrae and rib cartilage.

What does the myotome form?

Skeletal muscles (back, ribs, limbs).

What does the dermatome form?

Dermis of the back.

What regulates somitogenesis timing?

Clock and wavefront mechanism (FGF, Wnt, Notch signaling).

What is the role of FGF in somitogenesis?

High posterior gradient maintains undifferentiated cells.

What is the role of retinoic acid (RA)?

Opposes FGF and helps define the wavefront.

What is Mesp2?

Transcription factor activated by Notch that defines somite boundaries.

What do EphA4 and ephrinB2 do?

Form boundaries between somites via cell signaling and cytoskeletal changes.

What is epithelialization in somites?

Mesenchymal-to-epithelial transition (MET) forming structured somites.

What controls somite identity?

Hox genes.

What signal induces muscle formation in somites?

Wnt + Shh → activates Myf5.

What induces sclerotome formation?

High Shh → Pax1 activation.

What happens to the notochord after vertebrae form?

Undergoes apoptosis.

What is epimorphin?

Protein that attracts sclerotome cells to form vertebrae.

What are myoblasts?

Muscle precursor cells.

What do myoblasts fuse into?

Myotubes.

What do myotubes become?

Myofibers (muscle fibers).

What is MyoD?

A key transcription factor that drives muscle differentiation.

What does Myf5 do?

Activates MyoD.

What role do FGFs play in muscle formation?

Promote proliferation of myoblasts

What triggers myoblast fusion?

Decrease in FGF levels.

What molecules help cell adhesion during fusion?

Cadherins and CAMs.

What are meltrins?

MMPs that mediate membrane fusion.

What is the role of IL-4 in muscle formation?

Recruits additional myoblasts to fuse.

What are satellite cells?

Stem cells that regenerate muscle after injury.

What are the two types of ossification?

Intramembranous and endochondral.

What bones form via intramembranous ossification?

Flat bones (skull, clavicle, mandible).

What is endochondral ossification?

Bone replaces a cartilage template.

What induces cartilage formation in endochondral ossification?

SHH and Pax1.

What transcription factor is critical for chondrocytes?

Sox9.

What happens during chondrocyte hypertrophy?

Cells enlarge and prepare for mineralization.

What does VEGF do in bone formation?

Attracts blood vessels.

What transcription factor drives bone formation?

Runx2.

What does Wnt signaling do in osteogenesis?

Upregulates Osterix → bone formation.

What structure gives rise to tendons?

Syndetome.

Where does the syndetome come from?

Sclerotome near myotome.

What gene is important for tendon development?

Scleraxis.

What signal guides muscle toward tendon?

Slit (tendon) binding Robo (muscle).

When does gut development begin?

Week 3-4 in humans.

What are the three regions of the gut?

Foregut, midgut, hindgut.

What connects the midgut to the yolk sac?

Vitelline duct.

What becomes the mouth opening?

Stomodeum.

What becomes the anus?

Proctodeum.

What germ layer forms the gut lining?

Endoderm.

What forms gut musculature?

Splanchnic lateral plate mesoderm.

What signaling gradient patterns the gut?

Retinoic acid + FGF → Shh gradient.

What does Shh do in gut development?

Induces Hox gene expression.

What happens to Wnt signaling in the foregut?

It is inhibited.

What structure separates the trachea and esophagus?

Tracheoesophageal septum.

When does the respiratory tract bud form?

Week 4.

What initiates lung development?

Laryngotracheal groove.