Development Flashcards
Skeletal muscle develops from
Paraxial mesoderm, head and some neck muscles originate from head mesoderm
Somites form the myoblasts that eventually form the body wall
Somites- way the embryo can temporarily hold together a group of precursor cell that form a specific structure in a specific place, temporary staging platform, they are transient structures
outer portion of the somite looks epithelial, 1st set of signals on that somite divide it into a dorsal part (stays epithelial) and a ventral part (scatters into dots)
The area around the somite (notochord and neural tube) signal
Dermamyotome
layer of cells migrate beneath it to form a red layer that becomes the myotome (from these ccells we get skeletal muscle precursors)
Embryonic origin
Paraxial mesoderm receives signal from developing neural tube and notochord to migrate, these precursors stay in the area
Primaxial muscle domain (muscle attach to scleratome-derived bones), the muscles that form the medial border of the myotome near the forming vertebral comlumn (intrinsic back, intercostals, prevertebral muscles
Abaxial muscle domain (other signals come from the lateral mesoderm that influence the lateral portion of the myotome, these will form muscle of venterolateral abdominal wall and limbs)
Skeletal muscle formation
Dorsomedial edge and lip of the dermomyotome are myogenic, medial cells are associated with vertebral comlumn and ribs
The middle becomes the dermis of the back,
Late group of cells come out before dermis precursors fully form (satellite cells, located between BM and membrane of skeletal muscle cells)
Myoblasts
secrete adhesive glycoprotein that allow them to fuse and form tubular cylindrical structure called the myotube (precursor to mature fiber)
Development events: gene expression (genes sets that turn on progressively, facilitate single cell to multinucleated myofiber transition. Muscle cell secretes actin and myosin which organize into filaments (differentiated muscle cell (muscle fiber) form)
All of this controlled be series of genes
Definitive muscles from pre muscle masses
change in fiber direction (myotomes form flat sheets and are oriented like our hands in pockets)
Fusion of adjacent myotomes (most muscle) longitudinal splitting, tangental splitting into layers, atrophy of a part
Spinal nerves innervate somite derived skeletal muscles of trunk and limbs
Dorsal primary rami–> epaxial muscles ( as spinal nerve comes out, it branches to two divisions, dorsal and ventral rami. Innervate the muscles of the back which have remained close to the general area of generation)
Ventral primary ramus–> limb and ventral body wall hypaxial muscles
by week 8 muscles have formed and located close to final position in the body
Absense of a muscle or part of muscle
Part of syndrome, usually unilateral
Poland sequence: absence of pec maj and minor (subQ fat and axillary hair deficiency, possible hypoplastic rib cage, lateral displaced, absent nipple, also some upper limb issues ( shorter segments, syndactly webs and brachydactylyl short), more common on right side
Prune belly syndrome: absense of ab muscles, undescended testicles, bladder and urinary tract defects, prenatal fluid accumulation in lower abdomen cause issues with development and muscle degeneration, after birth–> abdominal distention is reduced causing skin wrinkling–> hense Prune belly, almost exclusive to males
Torticollis
abnormal formation of sternocleidomastoid muscle, causes neck to shift to one side, congenital or acquired (birth injury via forceps delivery, secondary to infection or trauma to SCM), congenital cases have additional hip dysplasia usually right side is more affected
Progenitor tissue of skeletal tissue
Epithelial mesenchymal interactions are involved in sk tissue formation
Primary progenitor=mesenchyme comes from mesoderm or in the head and neck ectodermal neural crest
In the trunk: mesenchyme of skeletal comes from paraxial mesoderm (somites), and somatic mesoderm (lateral mesoderm). In the head (neural crest- ectomesenchyme), head mesoderm unsegmented paraxial mesoderm
master genes
Bone–> Runx2 (CBFA1B) gene–> osteoblasts, bone formation can be direct via intramembranous ossification. Most bone is made via endochondral ossification (starts from the middle of the cartilage model)
Cartilage–> sox 9 –> chondroblasts (form chondrification centers, both master genes are Tx factors that activate expression of other genes that facilitate bone or cartilage formation (genes ate Not patterning genes)
Development of supporting tissue is a multi step process
1st step of skeletal tissue formation –>condensation of preskeletal mesenchyme
Then signals turn on master genes: Epithelial mesenchymal interactions are usually involved in support tissue formation
AER/mesenchyme-limb, Neural tube/mesenchyme-skull,vertebrae, notochord mesenchy-skull vertebrae
Vitamin D action in Ca homeostasis and bone formation
Critical in bone and cartilage formation, Vit D increases intestinal absorption. Highest requirement in life are in pregnancy for infant and in puberty
Ossification centers
Areas in skeletal primordium where ossification begins:
Primary ossification center: initial center to appear (shaft of long bone, center of flat bone, appears at 7 weeks, bone may have one or more ossification centers
Secondary ossification center: appear in perinatal, post natal or post pubertal period. Located at the epiphysis of long bones, heads of ribs, these close in the 20s to 30s (under hormonal control of maturation estrogen, thyroid hormone)
Bone age= amount of epiphyseal cartilage retained (comparison of bone and chronological age=measuer of skeletal grwoth and maturation)
Generalized skeletal dysplasia
Mucopolysaccharidoses: storage deefect in synthesis, storage, or transport of some lysosomal enzyme–> substrate accumulation. Autosomal recessive–> results in bone formation defects–> irregularities and dwarfism
Marfans syndrome
Growth hormone: increase-> Gigantism, decreased: Pituitary infantilism
Thyroid hormone: decreased-> cretenism dwarf
Achodroplasia: type of chondrodystrophia autosomal dominant, failure of endochondral ossification and interference w/ epiphyseal plate development. Trunk is normal but limbs are short (bow leggedness seen), associated w/fibroblast growth factor receptor 3
Osteopetrosis: Osteoclast disease, these fail to resorb bone tissue, fudgeing over bone remodeling and modeling, vitamin D3 supplementation helps
Osteogenesis imperfecta: defect in type 1 collagen gene autosomal dominant usually, multiple fractures and other issues
Somitocoel
Cavity inside the somites, these cells contribute to formation of vertebral column, ribs, and sternum
Cells of the ventral side of the somite peel away and move toward the formin neural tube to form spinal cord. Cells start to surround the notochord, the cavity is effectively gone, whats left dorsally is the myotome. The scleratome cells migrate next to notochord. These cells are an aggregate of mesenchymal cells formed from the ventromedial half of a somite, precursor to bone, cartilage, and tendon. dorsal lateral half retain epithelial morphology and become the dermomyotome which includes the skeletal muscle precursor. Scleratome cells-> progentors of vertebrae
Resegmentation
Initial sclerotome tissue divides into a cranial loose portion and caudal denser portion
The dense lower portion will fuse with the loose portion below it–> forming a vertebrae unit
The resulting offset is important because it allows the proper muscle bone configuration to move the spine
5th somite is the beegining of the spinal column
Abnormal regionalization
fusion of cervical spine–> klippel-Fiel sequence. Short neck, low hairline, limited cervical spine, also associated w/ CV defects and hearing loss, other MSK stuff too
Sacralized and lumbarized vertebrae
Sacralization–> 5th lumbar vertebra is incorporated into sacrum
Lumbarization–> 1st sacral vertebra is not included in the sacrum (number of vertebrae isnt changed)
dysraphism
Open vertebral column due to failure of fusion of spinous processes
Rachischisis: many or all vertebrae have unfused spinous processes (extensive opening w/CNS involvenment)
Spina bifida: variation in length of opening, several subtypes
Somite myotomes
form skeletal muscle within limb
early limb is a bud that = ectoderm sleeve w/ mesenchyme in middle. Mesenchyme has 2 sources, somatic mesenchyme from somites
Step 1 : wk 4 limb field establishment, bilateral areas of somatic mesoderm, induced by specific gene expression
Step 2: limb buds located at specific axial levels, surface ectoderm coats the bud (the mesenchyme inside was from the lateral somatic mesoderm). Somite mesoderm will migrate into it to form skeletal myoblasts (and neural crest cells)
Ectoderm thickens at dorsal/ventral surface interface (Apical ectodermal ridge AER- signal for proper limb dev)
Step 3 elongation: wk 6 (digital rays from epithelial mesenchymal interactions at the AER/mesoderm)
Step 4 wk 5-9 proximal to distal (somatic mesoderm-condenses to form cartilage model of bone), (somite derived myoblast- migrate into limb to form sk muscle, nerves and vascular precursors migrate into limb
Limb development is patterned and development in occurs along 3 sets of linear axes simultaneously
Proximal-distal axis development:
bud to all those wacky segments (reciprocal signaling between the AER and the mesenchyme beneath- Wnt retinoic acid involved), mesenchyme induces the AER, sustains the AER, determines limb type
AER: maintains proliferating pool of mesenchyme cells for linear growth, Maintains anterior posterior signaling center called the Zone of polarizing activity, interacts with proximal distal and anterior posterior specific proteins to provide mesenchyme cells with position info
Mesenchyme adjacent to AER form segment specific skeletal elements, form fibrous CT
Anterior posterior axis development
digits develop w/ prexial and postaxial borders
Another signaling center controls AP patterning: Zone of polarizing activity (along posterior border of limb), Group of somatic mesoderm derive mesenchymal cells along the posterior border of the limb
Sonic hedgehog gene (Shh) mediates patternin, retinoic acid has the same effect as SHH
Hox gene combinatorial expression controls digit formation along the ap axis
Apoptosis plays a role in limb development, especially separation of digits, Facilitates separation of digital rays in distal limb caused by breakdown of AER in the interdigital region
Development along dorsal-ventral axis
influences skeletal muscles-myoblasts organize into dorsal and ventral premuscle masses
Nerual and vascular structure
Limb compartmentalization
Patterning along the dorsal-ventral surface is achieved by secreting factors Wnt 7a and Tx factors
Failure to form limbs
can be due to removal of the AER (duplication of AER –> segment duplication)
Amelia- all of limb missing
Meromelia- part of limb is missing
Transverse - truncation or amputation along the proximal distal axis
Longitudinal - only meromelia: limb absense may occur along AP axis, preaxial=Radius and digits 1-3, post axial (posterior)=ulna and digist 2-4 missing
Hemimelia= missing radius or ulna, missing tibia or fibia, the length of limb is fine, but function is lost
Oligodactylyl or lobster claw deformity-absence of limb structures in the median portion of the distal limb segment
Phocomelia- seal limb a rare hand and feet close to trunk, limbs undr dev ,thalidomide
