DEVELOPMENT OF

MESODERMAL ORGANS
[Cuento, Danganan, Dayahan, Echon, Samonte]
Introduction of the Mesoderm
➢ In higher vertebrates, it partitions into four zones:
▪ Notochord
▪ Paraxial mesoderm
▪ Intermediate mesoderm
▪ Lateral Plate mesoderm

➢ Lateral plate is subdivided by the coelom into two:

▪ Somatic mesoderm
▪ Splanchnic mesoderm

➢ Skeleton orignates from 3 regions:

▪ Neural crest
▪ Somites
▪ Limb buds and associated lateral plate
SOMITOGENESIS AND MYOGENESIS
Somitogenesis

➢ Formation of somites through a process of

anteroposterior segmentation of the paraxial
mesoderm

Myogenesis

➢ Formation of muscular tissue

NORMAL DEVELOPMENT OF SOMITES
➢ Somites: blocks of mesoderm located on
either side of the notochord in the developing
vertebrate embryo
➢ Pattern of somites: indication of a segmental
arrangement of a body pattern
➢ Paraxial mesoderm distinguished from
intermediate mesoderm by transcription
factors Foxc1 and c2
➢ Number of somites formed: indication of stage
of a vertebrate embryo
NORMAL DEVELOPMENT OF SOMITES

➢ In chicks, somites condense into EPITHELIAL SOMITES

➢ Fibronectin and N-cadherin increases with the formation of epithelial

somite; responsible for changes in cell adhesion

➢ Epithelial somite:

▪ Undergoes epithelial-to-mesenchymal transformation forming: SCLEROTOME

▪ Lateral part forms a plate: DERMOMYOTOME

● Subdivides into two parts: DERMATOME and MYOTOME

SEGMENTATION MECHANISM
➔ Segmental repeating pattern of somites induced by oscillation or clock operating in
conjunction with a spatial gradient; “Segmentation clock” & “wavefront”
➔ One cycle = one somite
▪ Clock
● Periodic expression of the Notch pathway components and its target genes: Hes
genes and Lunatic Fringe
● Period of cycle depends on the species
▪ Gradient
● Determines somite’s formation in an anterior-to-posterior sequence
● FGF8
➔ The clock and gradient cooperate to generate segments because both are involved in
regulating genes that control segmentation
SEGMENTATION MECHANISM
➢ Hes Genes ➢ Wnt3 A
▪ Encode bHLH transcription factors ▪ Serves a bridge pathway
▪ Homologs of Drosophila hairy
▪ Induces Notch Signal
▪ Involved in segmentation
▪ Activates Hes7 genes
➢ Lunatic Fringe
▪ Homologous to Drosophila fringe
▪ Codes for glycosyl transferase
▪ Formation of compartment boundaries
SEGMENTATION MECHANISM
➢ Notch Signaling Pathway
▪ Highly conserved cell signaling system present in most multicellular organisms
▪ Coordinates cell clocks and keep them synchronized
▪ Necessary for the maintenance of somite borders
▪ Allows for communication between two adjacent cells and can elicit many
downstream responses
▪ Regulates expression of genes that control formation and differentiation of somites
 Hairy1

Notch
FGF8 Wnt3 Ephrin4A
Axin L. fringe Hes7
Wavefront Bridge Clock
Segmentation
SUBDIVISION OF THE SOMITE
➢ Sclerotome

▪ Induced by the notochord and

ventral part of the neural tube

▪ Forms vertebra, ribs, tendons

▪ Dorsal part of sclerotome: Syndetome

▪ Sonic Hedgehog (Shh) – principal

signal; expressed in the
notochord and floor plate of
neural tube
SUBDIVISION OF THE SOMITE
➢ Resegmentation

▪ Vertebra formed from posterior half of the sclerotome combining with the anterior half
of the next most posterior somite

• Vertebrae end up half a segment out of phase with the original repeating
pattern

➢ Hox genes

▪ Controls the regional character of the vertebrae

SUBDIVISION OF THE SOMITE

▪Anterior boundary of Hoxc6

expression: Cervical to thoracic
▪ Anterior boundary of Hoxd10
expression: Lumbar to sacral
▪ Anterio boundary of Hoxd12
expression: Sacral to caudal
SUBDIVISION OF THE SOMITE
➢ Dermatome

▪ Arises in response to Neurotrophin 3 signal from the dorsal neural tube

▪ Forms the dorsal dermis

➢ Myotome

▪ Forms skeletal muscle

▪ Epaxial myotome: Region near the midline; forms the segmental body axis

▪ Hypaxial myotome: Lateral region; forms the muscles of the ventral body
wall, limbs, and diaphragm
MYOGENESIS
➢ Skeletal muscle

▪ Derived from the myotomes of somites

▪ May also be derived from corresponding regions of the unsegmented head

mesoderm

▪ Consists of multinucleate microfibers

MYOGENESIS
➢ Differentiation of skeletal muscles:

Commitment of Multiplication Cessation of

cells to become and division to
migration form
myoblasts
myotubules
MYOGENESIS
➢ Smooth muscle

▪ Formed from both lateral plate mesoderm and hypaxial part of somites
MYOGENESIS
➢ Cardiac muscle

▪ Formed from the myocardium of the early heart; derived from anterior splanchnic
mesdorm
MYOBLAST FUSION
➢ Fusion depends on various molecules

▪ Inhibition of fusion by treatment with specific antibodies

▪ Fusion by transfection of appropriate genes

➢ In chimeric mice, myoblasts fuse to form one myofiber

➢ In Drosophila embryos, 30 multinucleate fibers arise

▪ Each initiated by a founder cell

MYOBLAST FUSION
➢ Founder myoblasts

▪ Express a cell-surface molecule: kinof-iireC (Kirre)

➢ Mammalian Muscle Fusion

▪ Mostly mouse C2C12 cells

▪ FGF removed - Fuses into MYOTUBULES

▪ FGF maintains expression of the transcriptional repressor Msx1

MYOGENIC TRANSCRIPTION FACTORS
➢ Transcription factors of the bHLH class:

○ MyoD, Myf5, Myogenin, MRF4

➢ bHLH factors act as dimers

○ E protein

➢ Inhibitory HLH

○ Contains dimerization not transcriptional activation; sequesters bHLH proteins

MYOGENIC TRANSCRIPTION FACTORS
➢ MyoD

○ Activates genes for some muscle proteins

○ Activates it own transcription

○ Upregulated in the hypaxial myotome

➢ Myf5

○ Initially upregulated in epaxial myotome

○ Knockouts of either genes (MyoD and Myf5) have slight effects on muscle
development

○ Double knockout of Myf5 and MyoD = severely affected mouse lacking both
myoblasts and skeletal muscles
MYOGENIC TRANSCRIPTION FACTORS
➢ Myogenin

○ Expressed all over myotome

○ Knockout causes a serious defect of skeletal muscle formation

➢ Myofibers may survive for the entire life of the animal

○ Muscles may increase in size only by enlargment of pre-existing fibers

➢ Growth

○ Controlled by feedback system: Myostatin

MYOGENIC TRANSCRIPTION FACTORS
➢ Muscle Satellite Cells

○ Small, monuclear cells

○ Originate from the central part of the dermomyotome

○ Expression of the transcription factor Pax7

○ Responsible for growth in fiber number

○ Repair of fiber