Lecture - Mesoderm Development

Objectives

Mesoderm formation

• Understanding of events during the third week of development
• Understanding the process of early somite development
• Understanding the process of body cavity formation
• Brief understanding of the future fate of mesoderm components
• Brief understanding of early heart formation

Notochord (Axial mesoderm)

• 

  Stage 7 embryonic disc

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  Stage 7 primitive-streak-node

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  Stage 7 cloacal-oral-membranes

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  Stage 7 notochord

Mesoderm

Stage 7 mesoderm

• • generated from epiblast cells migrating through the primitive streak
  • epiblast cells expressing fibroblast growth factor (FGF2)
  • forms a layer between ectoderm and endoderm with notochord down midline
  • present before neural tube formation
• divides initially into 3 components

• 

  Stage 7 paraxial mesoderm

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  Stage 7 intermediate mesoderm

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  Stage 7 lateral plate

• Paraxial mesoderm - somites - musculoskeletal structures
• Intermediate mesoderm - kidney
• Lateral plate mesoderm - body wall structures

Mesoderm Development

The trilaminar embryo

The four images below beginning at week 3 show cross-sections of the trilaminar embryo and the sequence of mesoderm development.

Mesenchyme

• Embryonic connective tissue, describes the cell morphology (Histology is not epithelial organization)
  • epithelial to mesenchymal transitions
  • mesenchymal to epithelial transitions

Paraxial Mesoderm

Hamburger & Hamilton Stage 10 (33 hours)

lies adjacent to notochord and forms 2 components Head - unsegmented paraxial mesoderm Body - segmented paraxial mesoderm Generates trunk muscles, skeleton, dermis of skin, blood vessels, connective tissue Segmented Paraxial Mesoderm segments called somites first pair of somites (day 20) segmentation imposes a pattern on nerves, vasculature, vertebra.... somites appear in ordered sequence cranial to caudal appearance so regular used to stage the embryo (Hamburger & Hamilton 1951- chicken) thought to be generated by a "clock" (1 pair every 90 minutes) neural tube begins to close at 4th somite level, 44 pairs of somites

Somite Formation

Carnegie stage 9 scanning electron microscope image showing somite formation

Early somite induction signals in the mouse

• ball forms through epithelialization and interactions (cell-cell, cell-extracellular matrix, ECM) fibronectin, laminin
• has 2 populations of cells - peripheral columnar and central mesenchymal
• early somite has cavity- somitocoel, cavity is lost during growth
• somite enclosed by ECM connected to nearby tissues

Somite Specification

• Different segmental level somites have to generate different segmental body structures?
• somite has to form different tissues?
• Somite Differentiation
• Compartmentalization accompanied by altered patterns of expression of Pax genes within the somite

Somite initially forms 2 main components

• • ventromedial- sclerotome forms vertebral body and intervertebral disc
  • dorsolateral - dermomyotome forms dermis and skeletal muscle

Somite Axial Specification

• rostro-caudal axis appears regulated by Pax/Hox expression, family of DNA binding transcription factors
• Movie: Somite Development

Sclerotome

• sclerotome later becomes subdivided
• rostral and caudal halves separated laterally by von Ebner's fissure
  • half somites contribute to a single vertebral level body
  • other half intervertebral disc
• therefore final vertebral segmentation ‚"shifts"

Dermomyotome

• later divides into dorsal dermatome and ventral myotome
  • (MH - This topic of muscle and skeleton development will be covered in 2 later lectures Musculoskeletal Development and Limb Development)

• lateral myotome edge migrates at level of limbs
• upper limb first then lower
• mixes with somatic mesoderm
• dermotome continues to contribute cells to myotome

Myotome

• Myotome component of Somite
  • epaxial myotome (dorsomedial quarter) forms the dorsal epimere (erector spinae)
  • hypaxial myotome (dorsolateral quarter) forms the ventral hypomere, 3 primary muscle layers which are different at neck, thorax and abdomen

Stage 14 Embryo showing somites and limb buds (Week 5)

Muscle

• Myoblast determining transcription factor MyoD is first expressed in the dorsomedial quadrant of the still epithelial somite whose cells are not yet definitely committed
  • basic Helix Loop Helix
  • from myotome

Muscle Development Abnormalities

• Duchenne Muscular Dystrophy
  • Embryonic muscle development normal and changes occur postnatally
  • X-linked dystrophy, large gene encoding cytoskeletal protein - Dystrophin
  • progressive wasting of muscle, die late teens
• Becker Muscular Dystrophy, milder form, adult onset

Axial Segmentation - Somite Specification Signals

Intermediate Mesoderm

lies between paraxial and lateral mesoderm generates urogenital system Wolffian duct, kidney MH - covered in Kidney Development Lecture/Laboratory

Lateral Plate Development

• lying at the surrounding edge of he embryonic disc
• a cavity begins in this week to form within the mesoderm itself

Intraembryonic Coelom

• small spaces (vacuoles) begin appearing within the lateral plate mesoderm
• small spaces enlarge forming a single cavity within the lateral plate mesoderm
  • divides lateral plate mesoderm into 2 parts at about day 18-19
• this cavity is called the Intraembryonic Coelom
  • coelom is a general term for a "cavity" and can lie within the embryo (intraembryonic) and outside the embryo (extraembryonic)
  • later anatomical spaces within the embryo and fetus can also be described as coeloms
• when the embryonic disc folds the intraembryonic coelom will form all 3 major body cavities:

1. Pericardial
2. Pleural
3. Peritoneal

Somatic Mesoderm

The intraembryonic coelom divides the lateral plate into 2 portions

• closest to ectoderm
• body wall osteogenic, chrondrogenic and fibrogenic
• except ribs and scapula

Splanchnic Mesoderm

• closest to endoderm
• heart, smooth muscle of gastrointestinal tract (GIT) and blood vessels

Carnegie Stages: 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 | 19 | 20 | 21 | 22 | 23 | About Stages | Timeline

Somitogenesis

Somitogenesis

Stage	Days (approx)	Size (mm)	Images (not to scale)	Events
7	15 - 17 (week 3)	0.4		gastrulation, notochordal process
8	17 - 19	1.0 - 1.5		primitive pit, notochordal canal
9	19 - 21	1.5 - 2.5		Somite Number 1 - 3 neural folds, cardiac primordium, head fold
10	22 - 23 (week 4)	2 - 3.5		Somite Number 4 - 12 neural fold fuses
11	23 - 26	2.5 - 4.5		Somite Number 13 - 20 rostral neuropore closes
12	26 - 30	3 - 5		Somite Number 21 - 29 caudal neuropore closes
13	28 - 32 (week 5)	4 - 6		Somite Number 30 leg buds, lens placode, pharyngeal arches
Stage 13/14 shown in serial embryo sections series of Embryology Program