module 9: mesodermal differentiation

gastrulation (chickens)

• blastodisk: initial divisions, always tilted-gravity determines orientation,

• mesoblastic discoidel

cytokinesis furrow

part of meroblastic discoidel cleavage in chickens

subgerminal cavity

space between the yolk and the epiblast layer where the hypoblast develops

koller’s sickle

more dense area of cells underneath the area pellucida, occurs after laying, where the primitive streak grows from

area opaca

outer layer of the embryo

area pellucida

the inner area of the embryo

epiblast

ectoderm + mesoderm + endoderm

specification of the primitive streak stage 1

• wnt8c is expressed around marginal zone

• vg1 (TGFb ligand) expressed on posterior side marginal zone

• cerberus expressed from hypoblast —> seqeusters and inhibits wnt8c and Vg1

specification of primitive streak stage 2

• proliferation of cells from area opaca form the endoblast next to the hypoblast —> pushes cerberus expression farther away allowing wnt8c and Vg1 activation

• expressed wnt8c and Vg1 + FGF expressed from the growing Koller’s sickle —> activate NODAL (TGFb)

specification of primitive streak stage 3

• NODAL expression defines the primitive streak

• NODAL forms the organizer: organizes cells into mesodermal and endodermal cells (needed and sufficient for orientation of embryo)

Hensen’s node

• signaling center

• node between notochord and primitive streak (AP)

• the most anterior side of the primitive streak

primitive streak development

1. migration: streak moves from posterior to anterior side , mesoprogenitors enter through ingression

2. regression: entire streak regresses from the anterior back to the posterior side

   1. the notochord is left behind — acts as a zipper that leaves behind the dorsal axis

AP border region: early

• Anterior: DKK-1 (dickopf-1) = wnt agonist

• posterior: Wnt

  • positive feedback loop: Wnt→activates Fgf8→activates wnt8c→ activates wnt

absence of wnt = head // wnt = posterior

AP border region: later

• Anterior:

  • expressing retanoic acid (morphogen)

  • RA inhibits Fgf8

• posterior:

  • Wnt majority → activates RALDH2 (releases retanoic acid)

  • wnt expresses fgf8 -→ inhibits RA

retinoic acid signaling

1. retinol + retinol binding proteins → retinol transporter into cell

2. retinol gets turned into retinaldehyde (via retinol dehydrogenase)

3. retinaldehyde into retinoic acid (via RALDH2)

retinoic acid 2 paths

1. RA enters neighbor cell → RA binds RAR (RA receptor) + RXR (reinoid receptors) -→ enter nucleus, bind RARE (RA response elements) → activates transcription

2. RA is degraded (via cyp26, cytochrome P450) → RAR+RXR bind RARE → but no transcription

mesodermal regionalization

1. axial mesoderm

2. paraxial mesoderm

3. intermedial mesoderm

4. lateral plate mesoderm

axial mesoderm

notochord (transient) —> intervertebral disks

paraxial mesoderm

• dermomyota → skeletal elements, dermis, skeletal muscle

• sclerotome → tendons, vertebral structures (proximal ribs), endothelial cells, aorta

intermedial mesoderm

kidneys, gonads

lateral plate mesoderm

• somatic: pelvis, limb bones

• splanchnic: vessels, blood, heart

blastocyst

blastula for mammals. trophoblast + inner cell mass (embryonic stem cells)

trophoblast

• syncytiotrophoblast —> placenta, invade endometrium

• cytotrophoblast

inner cell mass ICM

• epiblast: embryo proper + mesoderm extra

• hypoblast: primitive endoderm → yolk sac