Paraxial and

Intermediate

mesoderm

Paraxial Mesoderm

• Forms the back of the embryo, along

the spine

• Somites - a series of dorsal paired

segments occurring along the

notochord in vertebrate embryos.

Somite Derivatives

Somitogenesis

Periodicity

Somites are formed by a “clock and wave” mechanism:

Oscillating signal (clock) is provided by Notch and Wnt

pathway

Rostral to caudal gradient provides a moving “wave” of an FGF

With each wave of gene expression, another somite is formed

Separation

Ephrin tyrosine kinase

receptors (Eph A4) and

their ligands (Ephrin B2)

are able to elicit cell- cell

repulsion between

posterior somite and

migrating neural crest

cells.

Epithelialization

• A formed somite is

surrounded by

epithelial cells.

• Synthesis of

extracellular matrix

proteins, Fibronectin

and N-cadherin.

• Paraxis gene encodes

for the transcription of

the ECM proteins.

Specification

• Each somite forms a specific type of

vertebrae

• Tissue specified by:

– notochord (Shh)

– neural tube floor plate (Shh)

– neural tube roof plate (Wnts)

– lateral plate mesoderm (Fgfs)

Axial specification

Somites are specified according to the Hox genes they

express

Thoracic somite

Differentiation

• Sclerotome - cartilage of vertebrae and part of rib

• Dermamyotome - remaining portion of the somitecontains precursors for:

• Dermatome – dermis (mesenchymal connective tissue of the skin)

• Myotome – muscle

• Primaxial (epaxial) myotome – intercostal muscles of the ribs; deep muscles of the back

• Abaxial (hypaxial) myotome – body wall, limbs, tongue

Determination of Somites

Sclerotome – Shh (high) from the notochord and neural tube floor plate

- Sclerotome cells secrete Pax1 (transcription factor) cartilage/ vertebrae formation

Dermatome – neurotrophin3 (NT3) and Wnt1 from neural roof plate, forms dermis

Myotome: Abaxial - Wnt1, Wnt3a from the neural tube

Primaxial - Shh (low), Wnt (epidermis) + BMP4 (lateral plate mesoderm)

Notochord : degenerates through apoptosis (remnants remain as nucleus pulposus)

Myogenesis

• Specification and differentiation of

myogenic BHLH (basic helix-loop-helix)

proteins: MyoD and Myf5

• Muscle cells come from primaxial and

abaxial lineages in the somite

Osteogenesis

Bones

– The skeleton is generated from:

• Somites→ vertebrae

• Lateral plate mesoderm → limb bones

• Neural crest cells → brachial arch, craniofacial

bones

• Intramembranous Ossification

– The direct conversion of mesenchymal tissue into bone

– This process occurs primarily in the bones of the skull

• BMP activate Cbfa1,

a transcription factor

that transforms

mesenchymal cells to

osteoblasts

• Absence of Cbfa1 is

the elimination of

ossification

• Endochondral Ossification

– Mesenchymal cells differentiate into cartilage,

and this cartilage is later replaced by bone.

– Bone formation characteristic of the

vertebrae, limbs, and ribs.

• Blood vessels invade the cartilage model; hypertrophic chondrocytes die; replaced by osteoblasts

• ECM mineralizes • New bone material added

peripherally from the internal surface of the periosteum

• Osteoclasts (lateral plate mesoderm) hollow internal region bone marrow cavity

Intermediate Mesoderm

Kidney

• Nephron – functional unit, contains over

10,000 cells with at least 12 different cell

types

1. Pronephros

- pronephric duct arises in

the intermediate mesoderm

- duct cells migrate caudally

- anterior of the duct induced

the adjacent mesenchyme

to form pronephric tubules

- pronephros forms

functioning kidney of fish

larvae and amphibian

larvae

as the pronephric tubules degenerate, middle portion of nephric duct induces a new set of kidney tubules in the adjacent mesenchyme:

2. mesonephros

- as more tubules are induced caudally, anterior tubules begin to regress via apoptosis

- mesonephros function as one of the main sources of the hematopoietic stem cells

3. metanephros - permanent kidney of

amniotes

- metanephrogenic mesenchyme is

committed and forms in the posterior

regions of the intermediate mesoderm

- induces the formation of a branch from

each of the paired nephric ducts

- ureteric buds eventually separate form the

nephric duct; become collecting ducts and

ureters - take urine to the bladder