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Musculoskeletal DevelopmentIn this chapter you will begin to study musculoskeletal morphogenesis. The skeleton not only serves as an important framework and site for muscle deployment, but also provides protection for many other important organ systems. Additionally, it is an important site for calcium storage, an important metaboilte. The muscles are the motor machines of the body that support the skeleton, move it, and are important heat generating organs. Learning objectives are as follows:

• Reviewthebasicsofbonebiologyanditscloselyassociatedsystem,thejoints, as well as the basic arrangement of muscles in the body.

• Understandthedevelopmentalemergenceofthethesomiteandtheassociated cell movements during somitic morphogenesis and the formationofmusclefibers.

• Understandthestagesinvolvedintheformationofthevertebralcolumn and rib cage, along with its musculature.

• Understandthemorphogenesisoftheappendicularskeletonanditsmuscles.

• Understandthebasicsofendochondralandintramembranousboneformation.

• Understandthedevelopmentalprocessesofskullformation,thedevelopment of the facial skeleton, and the formation of the head musculature.

What can be more curious than that the hand of man, formed for grasping, that of a mole for digging, the leg of a horse, the paddle of the porpoise, and the wing of the bat should all be constructed on the same pattern and should include similar bones, and in the same relative position?

Charles Darwin, 1859

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Anatomy ReviewReview the basics of the musculoskeletal system

Skeletal ReviewYou should understand the basic anatomy of the following:Bones and joints of the skeletal system

Bones and joints of the skull

Bones and joints of the postcranial axial skeleton

Bones and joints of the appendicular skeleton

Anatomy of the synovial joint

Anatomy of a typical long bone

Muscle ReviewDesign of skeletal musclesYou should understand the relations of connective tissue and muscles cells within the design of a muscle.Muscle groups of the headYou should understand the basic layout of the muscles in the body.

Somitic musclesExtraocular muscles

Tongue muscles

Branchial arch musclesMuscleofthefirstbranchialarch

Muscle of the second branchial arch

Muscles of the third branchial arch

Muscles of the fourth and sixth branchial arch

Muscles of the caudal branchial arch

Muscle groups of the trunk wallEpaxial muscles

Superficialmuscles

Deep muscles

Hypaxial musclesSubvertebral muscles

Four-layered lateral wall muscles

Ventral muscles

Limb musclesMuscles annexed from the body wall

Ventral muscles

Dorsal muscles

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Development of the Paraxial MesodermParaxial mesoderm after gastrulation

Emergence of somitomeres

Differentiation of the somitesEpithelial somites

Segmental mesenchymal sclerotomes

Segmental dermamyotome epithelial plate

Sclerotome Migration and DifferentiationMigration of the sclerotomeRole of differential growth

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ResegmentationLoose cranial half

Dense caudal half

Relationstodermamyotomeandspinalnerve

Mesenchymal (blastemal) costovertebral elementDevelopment during the 4th and 5th embryonic weeks

Ventral to developing neural tube

Dorsal to the neural tube

In the body wall

Cartilaginous costovertebral skeletonSixth to eighth weeks of embryonic development

Body centers

Neural arch centers

Costal centers

Fusion of cartilage centers

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Boney stage of costovertebral developmentEighth embryonic week to 25 years

Primary ossification centersCentrum

Vertebral arch

Costal elements

JointsNeurocentral joints

Costovertebral joints

Secondary ossification centersSpinous process

Transverse processes

Annular epiphyses

Development of associated structuresIntervertebral discs

Periosteum and ligaments

Segmental variation

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Development of the SternumMesenchymal condensations of lateral somatic mesodermPaired sternal bars

Chondrification and fusion

Ossification centersManubrium

Sternebrae

Xiphoid process

Morphogenesis of the MyotomeTerminology

Role of body mesenchyme in muscle differentiation

Muscle cell formationMyoblast

Myotube

Myofiber

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Trunk muscle patternsEpaxial muscles

Layers

Hypaxial musclesSubvertebral muscle

Four-layered lateral muscle wall

Ventral muscle

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Postnatal trunk musclesRecallthattheembryonicpatternsthatarisesfromthesomitesisfoundinthe adult trunk. There are epaxial muscles with deep, intermediate, and superficiallayers,andhypaxialmuscleswithventral,four-layeredlateral,andsubvertebral muscle components.

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Development of Limb Skeleton - OverviewBasic featuresLimb bud

Lateral (somatic) mesodermMesenchymal (blastemal) stage

Cartilaginous stage

Endochondral bone formation

Limb FieldConcept of a morphogenetic field

Agroupofcellswhosepositionandfatearespecifiedwithrespecttothesamesetofboundaries.Aparticularfieldofcellswillgiverisetoitsparticular organ when transplanted to a different part of the embryo, andthecellsofthefieldcanregulatetheirfatestomakeupformissingcellsinthefield.

Limbs as morphogenetic fieldsMesodermal cells of the vertebrate limb can be identified by:

1) removing certain groups of cells and observing if a limb develops in their absence;

2) transplanting certain cells to a new location and observe whether they form a limb;

3) marking groups of cells with labels and observing which descendant cells partake in limb development.

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Factors in Limb Bud DevelopmentMesodermal outgrowthFibroblastic growth factor – the limb bud inducer

Block experiments

FGF soaked bead experiments

Apical ectodermal ridge (AER)What is it?

Role of AER:1) maintain the mesoderm beneath it in a plastic, proliferating phase that enables linear growth of the limb;

2) maintain the expression of those molecules that generate the anterior-posterior (thumb-pinky) axis;

3) interacting with proteins specifying the anterior-posterior and dorsal-ventral axes so that each cell is given instructions on how to differentiate.

Progress zone – the mesodermal componentWhat is it?

Relation to progress zone

Proximodistal growth and differentiationTime in the progress zone

Apoptosis in limb formation

Implications in vertebrate limb diversity

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AER

AER

AER

AER

RemoveAER 20 hours Humerus

forms

RemoveAER

RemoveAER

RemoveAER

20 hours

20 hours

20 hours24 hours

Add beadwith salinesolution

Add beadcontainingFGF2

Add beadcontainingFGF2

ImplantsecondbeadcontainingFGF2

Bead

Humerusforms

Humerus

Bead

Radius

Ulna

HumerusRadius

Ulna

Carpals

Digits

Secondbead

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Bone and Joint Formation in the LimbLateral plate mesenchymeMost limb bones

ExceptionsScapular body and spine

Blastemal stageMesenchymal condensation

Chondrification

OssificationProcess of endochondral bone formation

Cartilaginous anlage

Diaphyseal collar

Spread of diaphyseal collar and medullary cavity formation

Epiphyseal centers

Growth plate

Fusion

Cartilage Anlage Primary Ossification Center

Spread of Primary Center Secondary Ossification Center

CrossSections

CrossSections

New bone deposition

New bone deposition

Mitotic cartilage cells

Mitotic cartilage cells

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Joint formationCondensed mesenchyme

Undifferentiated zoneModifications

Synovial joints

Cartilage joints

Fibrous joints

Muscle Formation in the LimbMyotomal epithelial plate of somiteInduced by lateral plate mesoderm

Migrations of presumptive muscles cellsDorsal muscle masses

Ventral muscle masses

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Differentiation of muscle massesRelation to bone formation

Annexation of body wall muscles

Growth onto body wall

Limb rotation

Relation of muscle cells and connective tissue

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Morphogenesis of the Cranial BonesThree developmental anlage give rise to the cranium

Blastemal craniumThree centers to emerge

Chondrocranium or cartilaginous neurocranium

Dermatocranium or membranous neurocranium

Splanchnocranium or viscerocraniumCartilaginous splanchnocranium

Membranous splanchnocranium

Chondrocranium or cartilaginous neurocraniumEndochondral bones

Support for developing brain and special sensory structuresParachordal cartilages or basal plate

Supports brainstem

Fromoccipitalscleretomesandfirstcervicalsclerotome

Becomes basi-occipital bone

Hypophysial cartilageSupports pituitary gland

From neural crest

Becomes body of sphenoid bone

Trabeculae cranii or prechordal cartilagesSupports olfactory lobe of brain

From neural crest

Becomes body of the ethmoid bone

Nasal capsuleSupports nasal epithelium

From neural crest

Becomes conchae and perpendicular plate of ethmoid and inferior nasal conchae

Ala orbitalis and ala temporalisSupports developing eye

From neural crest

Becomes lesser wing and part of greater wing of sphenoid bone

Otic capsulesSupports inner ear anatomy

From neural crest

Becomes petrous and mastoid parts of the temporal bone

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Ossification of the chondrocraniumBone centers

Synostosis

Sutures

Dermatocranium or membranous neurocraniumDermal or intramembranous bones

Formation of calvarium

Fontanelles

Sutures

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Splanchnocranium or viscerocraniumThis series of skeletal elements arise from the interesting region known as the branchial or pharyngeal arches of the developing embryonic head. (See the following page for branchial arch development.) The middle ear ossicles, the jaw bones, the hyoid bone, and the cartilages of the larynx arise from the skeletal elements of these arches. Some of the bones form endochondrally from the cartilages of the arches, while others form as intramembranous ossificationsaroundcartilageprecursors.Theskeletalelementsarerepresented in the illustration below. Neural crest origin

Cartilaginous viscerocranium or derivatives of cartilaginous archFirst arch

Malleus, incus, and condyle and mentum of mandible

Second archStapes, styloid process, and lesser horn and superior body of hyoid bone

Third archGreater horn and inferior body of hyoid bone

Fourth and sixth archesThyroid, cricoid, and arytenoid cartilages

Membranous viscerocranium or intramembranous bonesMaxillaryprominenceoffirstpharyngealarch

Squamous temporal bones, maxillary bone, and zygomatic bones

MandibularprominenceoffirstpharyngealarchMost of the mandible

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Pharyngeal or Branchial ArchesComparative aspects of vertebrate heads

Pharyngeal arch designCraniocaudal patterning

Emergence of the phryngeal archesNeural crest tissue

Bone and connective tissue

Paraxial mesoderm (somitomeres)Skeletal muscles

Anatomy of the pharyngeal archesPharyngeal arch

Pharyngeal cleft

Pharyngeal pouch

Components of the archSkeletal elements

Muscle

Blood vessels

Cranial nerve

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Arch Development – Details of Skeletal ElementsFirst pharyngeal archIncus

Malleus

Anterior ligament of the malleus

Sphenomandibular ligament

Meckel’s cartilage

Second pharyngeal archStapes

Styloid process

Stylohyoid ligament

Lesser cornu and cranial part of the hyoid bone

Third pharyngeal archGreater cornu and inferior part of the hyoid bone

Fourth and sixth pharyngeal archesThyroid cartilage

Cricoid cartilage

Arytenoid cartilages

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Arch Development – Facial AnatomyEmergence of three key embryonic structures

Frontonasal prominenceNasal placodes

Lateral nasal process

Medial nasal process

Nasal pits

Intermaxillary process

First pharyngeal archMaxillary swelling or prominence

Nasolacrimal groove

Mandibular swelling or prominence

Second pharyngeal archCervical sinus

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Arch Development – Nasal and Oral CavitiesNasal RegionNasal placode

Nasal pit

Nasal sac

Nasal finOronasal membrane

Primitive choanae

Nasal septumCartilaginous and boney nasal septum

Nasal passagesConchae

Osseous sinuses

Definitivechoanae

Stomodeum

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Palate and oral regionPrimary palate

Median palatine process

Secondary palateLateral palatine processes or palatal shelves

Nasal septum

Median palatine process

Hard palateNasopalatne canal – Incisive fossa

Soft palateUvula

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Arch Development – External EarAuricle formationAuricular hillocks

ThreefromfirstarchHillock 1

Hillock 2

Hillock 3

Three from second archHillock 4

Hillock 5

Hillock 6

Contributions to postnatal auricleTragus

Hillock 1

Helix and cymba conchaHillocks 2 and 3

Antihelix and conchaHillocks 4 and 5

AntitragusHillock 6

External acoustic meatusFirst pharyngeal cleft

Meatal plug

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Arch Development – Middle EarFirst pharyngeal pouchTubotympanic recess

Distal expansion = tympanic cavity

Proximal part = pharyngotympanic tube

Tympanic membraneFirst pharyngeal membrane

Ectoderm

Endoderm

Mesodern

Middle ear ossiclesMalleus

Incus

Stapes

Middle ear musclesTensor tympani

Stapedius

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Arch Development – Tongue AnatomyFloor of first archMedian tongue bud or tuberculum impar

Distal tongue buds or lateral lingual swellings

Median sulcus

Floor of second archForamen cecum

Copula

Floor of third and fourth archesHypopharyngeal eminence

Laryngotracheal groove

Rima glottidis

Terminal sulcus

Occipital somites

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Arch Development – Skeletal Muscle AnatomyBasic arch design

Spread of the second archCervical sinus

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Muscle migration patternsFirst arch

Second arch

Third arch

Fourth and sixth arch

Caudal arches (pericardial ridge)

Somitic contributions

Resulting anatomy