MSK - Development Part I - (Kuhn) - JCN

What developmental structure induces differentiation of the somites? How does it do this?

*The notochord* By *Secreting developmental factors such as SONIC HEDGEHOG* (SHH)

TEST: What is the differentiation sequence of the hypaxial myotubes?

1) Delamination (from dermomyotome) 2) Migration 3) Proliferation 4) Determination 5) Differentiation

TEST: Somites further differentiate into what three components? About what week does this occur?

1) Dermotome 2) Myotome 3) Sclerotome Occurs during the 4th week

Give an example of the three different types of synovial joints

1) Interphalangeal joint 2) Knee joint 3) Sternoclavicular joint

Lateral plate mesoderm further differentiates into what two components?

1) Splanchnopleure 2) Somatopleure - outer body wall (vessels, skeletal tissue)

For BOARDS, what genes involved in connective tissue development are talked about more than others? What phase of development are each one involved in?

1) TGF-beta: Epithelial-mesenchymal interactions and condensation phases 2) BMP-4 - condensation phase 3) N-CAM, N-Cadherin - condensation phase 4) Pax-1 - Condensation/Differentiation phase 5) Fibronectin, Hyaluronan, Hyaladherin - Condensation/Differentiation 6) Collagen types II, IX, Cartilage proteoglycan -differentiation phase

Fusion of the physis doesn't occur until when?

18-25 YEARS

In What week does gastrulation occur?

3rd week

TEST: About what week do myoblasts first arise and begin to migrate?

5th week

Divisions of the muscle blestema begins to form around week ___

6

TEST: When does primary ossification usually start?

7-12 weeks

TEST: Each vertebral segment derives from how many somites? The upper part of each vertebra forms from what?

A part of *TWO separate somites* on either side of the notochord, for a total of 4 parts The UPPER part of the vertebra comes from the CAUDAL sclerotome of the somite above on either side of the notochord

TEST: The myotome layer gives rise to what?

All muscles of the body (hypaxial and epaxial)

When do secondary ossification centers FULLY develop?

Around puberty

TEST: Name the bones that develop from the Primary sclerotome

Axial skeleton: base of skull (endochondral bones), vertebrae, ribs, clavicle

What influences growth of LATERAL DORSAL Musculature? Medial Dorsal?

BMP = Lateral Dorsal WNT = Medal Dorsal

Secondary ossification begin from ___ and go to the ____ year

Birth - 9th year of life

OSTEOGENESIS IMPERFECTA presents with

Brittle bones Frequent fx ↓ Collagen → BLUE where sclera should be.

The ______ model of bone develops within the condensed ________ (cartilage begins as what?)

Cartilage model of bone develops within the condensed PREcartilage

The intramembranous bones of the skull develop from where?

Cranial NEURAL CREST

TEST: The dermotome layer gives rise to the ______

DERMIS

All muscles of the body come from the _____ layer of the ____ What week do they begin to MIGRATE to their FINAL LOCATION?

DERMOMYOTOME layer of the SOMITE *5th week*

AGAIN: The body wall muscles form from what part of the somite?

DERMOMyotome of SOMITE

In OSTEOGENESIS IMPERFECTA, what defect is present What are the genes associated?

Defect in Type I collagen Types I-IV = COL1A1 & COL 1A2 genes

TEST: The _____ of the bone develops first from the ______ ossification center

Diaphysis, PRIMARY ossification center

What is the function of HOX gene expression?

Differentially expressed as the limb grows to regulate BONE TYPE and SHAPE

TEST: The dorsal surface of the LE is (anteriorly/posteriorly) , while the ventral surface of the LE is (anteriorly/posteriorly)

Dorsal surface of LE is ANTERIORLY Ventral surface of LE is POSTERIORLY This is because of the rotation of the entire lower extremity at approximately mid-thigh

Which muscle group is more media? Which group forms body wall and limbs?

Epaxial - deep back Hypaxial - body wall/limbs

The dermamyotome goes on to form?

Epaxial and Hypaxial muscle

Developmental scoliosis occurs from an error in what?

Error in migration, resulting in missing parts of the sclerotomes (incomplete rostral and caudal sclerotomes) creating new "half-vertebra" and thus tilting the spinal cord

TRUE or FALSE: Joints develop after bones have formed and developed

FALSE, they form during bone formation/development

What gene initiates differentiation in tissues of the limbs? What gene is expressed on the outer edge of the limb bud that allows the limb to grow outward?

FGF-10 initiates diff of limb tissues AER on outer edge of limb, allows limb to grow outward

In Achondroplasia, there is an error in expression of ___

Fibroblast Growth Factor Receptor 3 gene (FGFR3)

TEST: Muscles migrate from _____ to _____, beginning with the (pre/post)-axial side first

From PROXIMAL to DISTAL Begins with the POSTaxial side first (dorsal or extensor side)

How do bones increase in width? What about in length?

Grows in width through deposition by osteoblasts on the OUTSIDE occuring MORE than resorption by osteoclasts on the INSIDE Grows in LENGTH via the epiphyseal growth plate

When a somite doesn't split apart a ___ is created. This can lead to?

HEMI-VERTEBRA Leads to DEVELOPMENTAL SCOLIOSIS

TEST: The myoblasts that migrate away from the dermomyotome to the *limb buds* form the ______ muscles, while the myoblasts that slide under the dermomyotome form the _____ muscles

HYPAXIAL (limb) muscles = migrating myoblasts EPAXIAL (deep back) muscles = myoblasts UNDER dermomyotome

TEST: Tendons appear to arise from the (origin/insertion) and migrate (proximally/distally) to the muscle

INSERTION, migrate PROXIMALLY

TEST: In the upper limb, the (dorsal/ventral) musculature extends all the way to the hand while in the lower limb, the (dorsal/ventral) musculature extends all the way to the foot

In UE, VENTRAL muscles extend to hand In LE, DORSAL muscles extend to foot

The splanchnopleure forms?

Internal organs Connective tissue Smooth muscle etc

What is club feet and what is it due to? When does it typically happen?

Inversion at subtalor joint, adduction at talonavicular joint, and plantar flexed Due to reduced motion in utero, so that the foot shape conforms to the uterine wall Typically happens during the 2nd trimester

The epiphyseal plate allows the bone to grow in ____

LENGTH

TEST: Bones develop together as a _____ ______, not as _______ bones and are connected by their ________

LINEAR SEQUENCE, not as ISOLATED bones Connected by their PERICHONDRIUM/PERIOSTEUM

What is ECTRODACTYLY?

Lobster claw Missing third digit of the hand

TGF-Beta mutations can cause____ syndrome, whos basic problem is with_____

MARFANS Fibrillin

Before the epiphyseal plate fuses, the bone is (more/less) subject to separation

MORE

AGAIN: Mesenchymal cells migrate at what weeks? What about condensation and chondrification?

Mesenchyme migration = 4th-5th week Condensation = 5th-6th week Chondrification = Beginning of 6th week

TEST: Myoblasts fuse into ______ which then fuse into _______ ______ fibers

Myoblasts --> MYOTUBES (primary then secondary) --> Skeletal muscle fibers

What does an individual with achondroplasia appear with?

Normal size trunk Short limbs Macrocephaly ↑ Lumbar Lordosis Spinal Stenosis

The upper and lower limbs of humans rotate in the (same/opposite) direction

OPPOSITE Elbows point backwards, knees point forwards

As cartilage forms, along the outside, ____ develops and connects between ___ to create a ___

PERIchondrium Between two bones to create JOINT CAPSULE

TEST: The somatopleure layer gives rise to what?

Peripheral skeletal elements (the rest of the body skeleton and rest of skeletal tissues)

Embryonic myoblasts go on to form?

Primary Myotubes

The vessels that start out supplying a limb are generally _____

REPLACED by other vessels

Each sclerotome is split into two parts, the _____ and ______ scelrotomes.

ROSTRAL and CAUDAL sclerotomes

Where is the intervertebral disk derived from?

Remaining MESODERM

What helps to determine the ATERIOPOSTERIOR and DORSOVENTRAL orientation?

Retinoic acid → Sonic HH Dorsoventral: Wnt7a Engrailed-1 Lmx1

The shock absorption effect of the vertebral column is that it is an ___

S-Shaped curve

Vertebral development comes from the ___ and chondrification is at roughly ___ weeks Primary Ossification centers develop when?

SCLEROTOME 6th week Primary ossification - 8th week

Only the ___ of the bones are ossified. The epiphyses would then, still be ______

SHAFTS = ossified Epiphyses = CARTILAGE

AGAIN: Vertebrae arise from what part of the somite?

Sclerotome, which is the most MEDIAL part

TEST: Secondary ossification centers in bone development generally BEGINS when? What part of the bone forms from this?

Shortly AFTER birth - 9th year, depending on bone Forms the EPIPHYSIS

AGAIN: The appendicular bones form from what developmental layer?

Somatoplure

What are meromelias? They are more common in children born to women treated with what?

Spectrum of missing limbs or parts of limbs Thalidomide

What forms in unison with the joint capsule?

Synovial Membrane

Where does the lower part of the vertebra come from?

The LOWER part of the vertebra comes from the ROSTRAL sclerotome of the somite below on either side of the notochord

TEST: The UE grows out 90 degrees (ventrally/dorsally) and the muscles ventral to limb bones are (pre/post)axial

UE 90 degrees DORSALLY Muscles VENTRAL to limb bones = PREaxial

The first mesoderm is _____

Undifferentiated

The sacrum forms from the union of __ separate vertebral segments, with fusions beginning with the (highest/lowest) segments and ending with the (highest/lowest) segments

Union of FIVE separate vertebral segments Begins with the LOWEST segments Ends with the HIGHEST segments (BOTTOM UP)

TEST: The sclerotome layer of the SOMITE gives rise to what?

Vertebral column and discs

TEST: The human stance with the upper and lower limbs are similar to a reptiles. Explain this stance and explain how we ended up being DIFFERENT than the reptilian stance.

We started out with elbows and knees splayed out, hands and feet facing outwards. Human elbows and knees are developmentally ROTATED ANTERIORLY to give us our final stance

What is polydactyly?

extra digits