Development

Question 1

Skeletal muscle develops from

Answer 1

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

Question 2

Dermamyotome

Answer 2

layer of cells migrate beneath it to form a red layer that becomes the myotome (from these ccells we get skeletal muscle precursors)

Question 3

Embryonic origin

Answer 3

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)

Question 4

Skeletal muscle formation

Answer 4

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)

Question 5

Myoblasts

Answer 5

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

Question 6

Definitive muscles from pre muscle masses

Answer 6

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

Question 7

Spinal nerves innervate somite derived skeletal muscles of trunk and limbs

Answer 7

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

Question 8

Absense of a muscle or part of muscle

Answer 8

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

Question 9

Torticollis

Answer 9

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

Question 10

Progenitor tissue of skeletal tissue

Answer 10

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

Question 11

master genes

Answer 11

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)

Question 12

Development of supporting tissue is a multi step process

Answer 12

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

Question 13

Vitamin D action in Ca homeostasis and bone formation

Answer 13

Critical in bone and cartilage formation, Vit D increases intestinal absorption. Highest requirement in life are in pregnancy for infant and in puberty

Question 14

Ossification centers

Answer 14

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)

Question 15

Generalized skeletal dysplasia

Answer 15

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

Question 16

Somitocoel

Answer 16

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

Question 17

Resegmentation

Answer 17

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

Question 18

Abnormal regionalization

Answer 18

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)

Question 19

dysraphism

Answer 19

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

Question 20

Somite myotomes

Answer 20

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

Question 21

Limb development is patterned and development in occurs along 3 sets of linear axes simultaneously

Proximal-distal axis development:

Answer 21

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

Question 22

Anterior posterior axis development

Answer 22

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

Question 23

Development along dorsal-ventral axis

Answer 23

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

Question 24

Failure to form limbs

Answer 24

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

Question 25

Failure of differentiation (separation of limb parts

Answer 25

Fusion of one or more digits=syndactylyl

Sironomelia- lower limbs fused together

Question 26

Duplication of limbs, overgrowth, undergrowth, congenital constiricion band,

Answer 26

Duplication: polydactylyl-autosomal dominant or recessive, usually bilateral. Diplopodia- duplication of portion of limb usually distal segment (could be due to AER duplications)

Overgrowth- limb hypertrophies as they develop

Undergrowth- hypoplasia of limb, Brachydactylyl- digit shortened due to lack of joints

Congential constriction band syndrome: during development pieces of amnion break away and wraparound forming limb–transvers amputation

Question 27

Lower limb fudge ups

Answer 27

club foot- any foot ankle defect involving the talus bone, talipes equinovarus=most common form, varus condition (foot is planar flexed, inverted, and adducted), multifactorial inheritance (smoking uterine pressure on abnormally placed foot genetics

Dev dysplasia of the hip: hip joint dislocates easily, increased in females, under dev of acetabulum

Question 28

Upper limb fudge ups

Answer 28

Sprengel deformity- undescended scapula–dysplastic (usually left scapula, can be bilateral), muscles of scapula are hypoplastic or atrophic (limits shoulder movement –disfigurement)

Cleidocranial dysplasia (individuals w/ CD–hypoplasia or aplasia of clavicles (usually bilateral, large head small head long neck drooping shoulders, and a short narrow chest, dental problems and short fingers, other anomilies that im too lazy to type out taking the hit on this one