muscle embryology Flashcards
gastrulation
the process of cell division and migration resulting in the formation of the three germ layers- ectoderm, mesoderm, endoderm.
mesoderm
- the building block of most muscle
- once the mesoderm layer is formed, it becomes divided into distinct regions
notochord
- signalling centre that contains mesoderm cells that have thickened up and controls the specification of surrounding cells
- signals to mesoderm and ectoderm (from the nervous system)
paraxial mesoderm
- adjacent to the notochord
extra-embryonic mesoderm
- important in development of the extra embryonic membranes
oropharyngeal membrane and cloacal membrane
- contains no mesoderm, no muscle development
- later on forms into the mouth or anus (cloacal)
mesoderm differentiation
occurs during days 17-21
day 19- mesoderm layer starts to develop fastest, pushing up the ectoderm.
- cells of the mesoderm are undergoing proliferation
day 20 - space from between lateral plate mesoderm and paraxial mesoderm
day 21- the space splits the lateral plate mesoderm into two distinct populations, upper portion of lateral plate mesoderm and lower portion, split by cavity/asylum.
paraxial mesoderm
- from from cells moving bilaterally and cranially from the primitive streak
- lies adjacent to notochord and neural tube
- from the somites (solid block of paraxial mesoderm) in the embryo
intermediate mesoderm
- forms the genitourinary system
lateral plate mesoderm
- split by a cavity (intraembryonic coelom) into two layers
1. somatic (top) or parietal layer (bottom)
2. splanchnic or visceral layer
muscle development from ectoderm
- smooth muscle- pupil, mammary and sweat glands
somite formation- somitogenesis
- paraxial mesoderm gets organised into segments- somites
- form alongside the developing neural tube in a craniocaudal sequence over time from day 20
- appear at approx 3 pairs a day until the ned of week 5
- can accurately determine the age of an embryo by the number of pairs
control of somitogenesis
- mesenchymal: epithelial transition
- unsegmented mesoderm- pre-somitic mesoderm, gets patterned
- many different molecular factors are involved in this patterning
- notochord influences somite formation
regulation of somitogenesis- clock and wave mechanism
- FGF family, Wnt, Notch: these genes/gene product tell cells to switch between a permissive and non permissive state in a constantly timed fashion
- a wave of factors then sweeps along the length of the merry and interacts with the cells that are permissive at the right time in the right area
somite clock and wave mechanism example
- clock gene expression (notch)
- once cells are at the right ‘time’ they express notch, allowing them to react to the wave.
helped along by Wnt - FGF 8 will only have an effect of making a somite if the mesoderm is at the right time and expressing notch
- somites are thought to form via the intersection of two activities known as the clock and the wavefront
5th week, somitogenesis
- by the end of the fifth week, 42-44 pairs are present
- these will go on to form the axial skeleton
somite differentiation- epithelisation
- segmented blocks of paraxial mesoderm are transformed into spheres
- epithelial cells around a lumen
- week 4
epithelial- mesenchymal transition
- once the somites have formed, they start to differentiate.
- cells in the ventral and medial area undergo an epithelial- mesenchymal transition- becomes the sclerotome, forms the vertebrae and ribs
- cells in the dorsal half form the dermomyotome
- dermoymotome further splits again to form: dermatome (dermis of the back), myotome (muscle)
myoblasts- muscle cell precursors
myocytes- mature muscle cells. They are made from myoblasts which are muscle cell precursors
- undergo cell division under the influence of growth factors
- when growth factors are depleted, myoblasts stop dividing
- myoblasts align into chains and fuse, cell membranes disappear- multinucleate myotubes- primary myotubes
- myogenic mediates this differentiation
muscle development regulation
- MYOD and MYF5: transcription factors, activate muscle- specific genes, enable the differentiation of myogenic precursor cells in the dermomyotome into myoblasts
- can convert non-muscle cells 9fibroblasts, adipocytes, chondrocytes, retinal pigment cells) to cells expressing all the muscle proteins i.e to muscle cells
molecular regulation of somite differentiation
neural tube- WNT proteins (activating) and BMP (inhibitory) combine to activate MYOD in the dermomyotome- creating a group of muscle cell precursors, which express MUF5
notochord- sonic hedgehog and noggin induce sclerotome formation
lateral plate mesoderm- WNT and BMP- activates MYOD/MYF 5 (activate muscle specific genes, pushes cells to become myoblasts)
MYOD1
- fibroblast and adippblats can be reprogrammed to become myoblasts if transfected with MYOD1 mRNA
MYF5
- requires for myoblast formation
- inactivated MYF5 in mice results in delayed development in the intercostal and paraspinal regions
MYF5 + MYOD1
- loss of function mutation results in a complete lack of skeletal muscle formation
histology slide (top to bottom)
-resting cartilage
- proliferation of chondrocytes
- maturation- no more mitosis
- zone of hypertrophy, cells enlarge and form vacuoles
- cartilage degeneration
- osteogenic activity
