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Sviluppo dello scheletro

The two major parts of the human skeleton are the axial (80 bones in skull, vertebra, ribs, sternum) and appendicular (126 bones in limbs, shoulders, pelvis) skeletons.

appendicolare assiale

• Cellule delle creste neurali (contributo mesoderma precordale)

(ossa del cranio)

• Sclerotomo dei somiti

(vertebre e coste)

• Mesoderma laterale somatico

(sterno)

Scheletro assiale o assile Mesenchima da:

sclerotomo

Mesenchima dal:

• Mesoderma laterale somatico

(ossa degli arti e dei cinti scapolare e pelvico)

Scheletro appendicolare

RA

M M

M

CEA

OSSIFICAZIONE

• Ossificazione diretta o membranosa

• Ossificazione indiretta

Ossificazione diretta

• Avviene durante la vita embrio-fetale per differenziamento delle cellule mesenchimali in osteoblasti; o durante il rimodellamento dell’osso anche nell’adulto a partire da cellule osteoprogenitrici

• Nell’embrione, le ossa che si formano con questo tipo di ossificazione sono le ossa piatte della volta cranica (porzione interparietale dell’occipitale, parietali, frontale, la porzione squamosa dei temporali);

• Ossa della faccia: mascella e mandibola, lamina mediale dei processi pterigoidei dello sfenoide, ossa nasali, lacrimali, palatine, osso zigomatico;

• Clavicola

Ossificazione indiretta e diretta delle ossa della faccia e del cranio

Una parte delle ossa della faccia (es: sfenoide,

e della base del cranio (es: temporali,

si abbozzano come cartilagine condrocranio) (ossificazione indiretta)

condrocranio

neurocranio

frontalee

parietale

mascellare

mandibolare

porzione interparietale

occipitale

futura fontanella inferiore

futura sutura coronale

osso nasale

osso lacrimale

osso zigomatico

grande ala sfenoide

condrocranio

anello timpanico osso temporale

frontalee

parietal

temporale

mandibola

mascella

grande ala sfenoide

nasale

PTH Vitamina D3 Prostaglandine

WNT

Osterix

ll differenziamento delle cellule

osteoprogenitrici (MSC) in osteoblasti

dipende dall’attivazione della via di WNT (b-

catenina) e dei “master genes” Runx2 (o

Cbfa1) e Osterix ( fattori di trascrizione)

WN

T

1

s

Runt-related TF-2

BGLAP gene osteocalcina

Ossificazione indiretta

• Le ossa si formano come cartilagine ialina e vengono sostituite da tessuto osseo

• Questo tipo di ossificazione avviene per alcune ossa del cranio (condrocranio): etmoide, vomere, quasi tutto lo sfenoide, squama occipitale, ossicini dell’orecchio, porzione timpanica e petrosa ossa temporali, osso ioide.

• Vertebre, coste e sterno

• Tutte le ossa dello scheletro appendicolare (eccezione clavicola)

occipitale

temporale

condrocranio

Temporale (parte timpanica e petrosa)

sfenoide occipitale (squama)

osso ioide

etmoide vomere

The sternum develops from the somatic mesoderm in the ventral body wall.

Le costole originano dai processi costali delle vertebre toraciche

pre-condroblasti

condroblasti

condrociti

PTH

Coll-II aggrecani

SOXs PAX-1 Scleraxis

BMPs

Mesoderma

cellule mesenchimali

TGF-beta

RUNX-2

aggregazione

proliferazione

differenziamento finale

Shh

FGFs IGF1

PAX-1-2 Scleraxis

Ihh

BMPs

WNT

osteoblasto

Embrione di 36-40 g colorazione alizarina

clavicola

femore

Il primo osso cartilagineo in cui compare un centro di ossificazione I è la clavicola

Vertebral column SPINA BIFIDA OCCULTA results from failure of fusion of the halves of the vertebral arch, most often in the lumber and sacral regions

It is a common defect but usually of no significance The skin over the bifid spine is usually intact, and there may be no visible signs of the defect except for a "dimple" or tuft of hair Severe types do exist and are described under Nervous system development

KLIPPEL-FElL SYNDROME (brevicollis): very rare; extreme shortening of the neck due to a reduced number of cervical vertebrae. The rest of the cervical vertebrae are usually abnormal in shape and may be fused. Associated with other abnormalities ASYMMETRICALLY FUSED VERTEBRAE or parts of vertebrae missing; an increase or decrease in vertebral number is not uncommon due to the complicated process of formation and rearrangement of the segmental sclerotomes in development

Ribs: defects are mostly secondary to malformations of the vertebral column IF PART OR ALL OF A VERTEBRA is missing, the corresponding ribs are generally gone IN SEVERE CONGENITAL SCOLIOSIS, the ribs on the concave side of the chest are often fused or branched ACCESSORY RIBS: usually the cervical rib (lumbar ribs are less common)

Attached to the seventh cervical vertebra; may be unilateral or bilateral Pressure effects on the brachial plexus or subclavian vessels may produce symptoms From retention and development of costal processes of cervical or lumbar vertebrae

FUSED RIBS: this may occur posteriorly when 2 or more ribs arise from a single vertebra Often associated with a hemivertebra which may produce scoliosis

Sternum CLEFT STERNUM

Minor clefts or notches are common and are seen as isolated anomalies Major clefts are usually associated with severe malformations of the chest Large clefts are rare ( heart); associated with herniation of thoracic viscera

The clavicles CLEIDODYSOSTOSIS: absence of all or part of the clavicle

Usually bilateral and the shoulders are drawn forward to meet under the chin Often associated with skull defects (cleidocranial dysostosis)

Skull malformations range from major defects incompatible with life to those that are

minor and relatively unimportant. The abnormalities are manifold, and either all or part of the skull may be involved. They are frequently associated with brain defects:

CRANIOSCHISIS OR ACRANIA: the cranial vault is almost absent and a large spinal defect is often present. Also associated with anencephaly

Due to a failure of the cranial end of the neural tube to close during week 4, thus the cranial vault does not form

CRANIOSYNOSTOSIS OR CRANIOSTENOSIS: due to premature closure of skull sutures More common in male than female; associated with other skeletal abnormalities Type of deformed skull depends on which sutures close prematurely

If sagittal suture: a long, narrow, wedge-shaped skull (scaphocephaly) If the coronal suture: a high, towerlike skull (oxycephaly or acrocephaly) If coronal or lambdoid suture closes on one side: twisted and asymmetric skull (plagiocephaly)

MICROCEPHALY: cranium is normal size or slightly small, but there is no abnormal closure of the sutures. It is primarily an abnormality of the CNS in which the brain and skull both fail to grow

Giantism

Hypopituitarism

Bone tissue diseases

La mutazione del gene per il

recettore FGF-R3 per FGF18,

iperattiva il recettore che avendo

una funzione inibitoria sulla

proliferazione dei condroblasti ne

riduce la proliferazione e provoca

acondroplasia Velazques, Sebastian de Morra

(Nanismo disarmonico)

ACONDROPLASIA

Osteogenesi imperfetta

(patologia genetica, autosomica dominante)

Mutazioni dei geni del collagene I (Col1A1 e Col1A2): le ossa fragili tendono a rompersi facilmente (altri difetti a carico dell’accrescimento dello scheletro, di cute, occhi, orecchie etc.)

Michel Petrucciani Michel Petrucciani

Difetti nella formazione o nelle funzioni degli osteoclasti portano ad un aumento della massa di tessuto osseo e causano una patologia

chiamata osteopetrosi

nell’osteopetrosi

Nanismo (nanismo armonico) e gigantismo ipofisario: carenza o eccesso di GH, rispettivamente

Short stature can be caused also by a defect in the growth hormone receptor (growth hormone resistance). Growth hormone resistance is also called Laron dwarfism. Growth hormone deficiency is treated with GH replacement; Laron dwarfism is treated with IGF-1 replacement.

Sviluppo della muscolatura scheletrica

Somitomeri (con contributo mesoderma precordale): muscoli della testa Miotomi dei somiti: muscoli estrinseci degli occhi, della lingua, del collo, muscoli del tronco e degli arti

NEW: Contributo del mesoderma laterale ad alcuni muscoli della testa e del collo

There are more than 640 skeletal muscles in the adult human body.

5-10 settimana di sviluppo

Somiti occipitali

Somiti cervicali

Somiti toracici

Somiti lombari

Somiti sacrali Somiti

coggigei

Somitomeri

lingua occhio

orecchio

(muscoli testa )

Miotomi (muscoli estrinseci degli occhi, della lingua, del collo, muscoli del tronco e degli arti)

Muscoli degli arti

somitomeri

som

iti

Head muscles originate from cranial paraxial mesoderm. Cranial paraxial mesoderm lacks any initial signs of segmentation and mesodermal cells will only be segregated once they reach the branchial arches concomitantly with cranial neural crest cells. Three distinct groups of cranial muscles can be

distinguished: the extraocular muscles, originating from the

prechordal mesoderm, the

branchiomeric muscles including the muscles of the jaw, anterior neck and face, arising from the paraxial

mesoderm and the tongue and posterior neck muscles,

deriving from anterior somites.

Muscoli della testa

The dorsomedial part of the

dermomyotome gives rise to the epaxial musculature corresponding to the back

and intercostal muscles, while the ventrolateral part of the dermomyotome

gives rise to the hypaxial musculature corresponding to the

diaphragm, abdominal and limb muscles. Few muscles from the most posterior part of the head, including tongue muscles and muscles of the posterior pharyngeal arches also develop from the somites.

Muscoli del tronco e degli arti

sclerotomo

IGF

Epiectoderma

PAX1

PAX1

SHH

MRF4

MRF4

SIX 1-2 (Sineoculis

homeobox homolog 1-4)

Le fibre muscolari scheletriche si formano prima della nascita e aumentano di volume durante lo sviluppo postnatale: -una fibra muscolare scheletrica è un sincizio ovvero una cellula derivata dalla fusione di diverse cellule singole:

i mioblasti nel caso della fibra muscolare

Cellula

mesodermica

Myf6

PAX-3

Stadi del differenziamento muscolare:

Myoblast - individual progenitor cells

Myotube - multinucleated, but undifferentiated

contractile apparatus (sarcomere)

Myofibre (myofiber, muscle cell) - multinucleated

and differentiated sarcomeres

•primary myofibres - first-formed myofibres, act as

a structural framework upon which myoblasts

proliferate, fuse in linear sequence

•secondary myofibers - second later population of

myofibres that form surrounding the primary fibres.

Mappa delle regioni della cute (dermatomi) e della muscolatura scheletrica (miotomi)

Myotomes

= regione della cute innervate da rami dello stesso nervo spinale sensitivo

= gruppi di muscoli innervati da rami dello stesso nervo spinale motorio

Sviluppo degli arti

IV settimana

• Ro

tazion

e degli arti

8th week

IV settimana V-VI settimana VII-VIII settimana

PAX-3+ cells (miotomi ipoassiali C3 e C4

e L3 e L5)

cellule mesenchimali dalla somatopleura: cartilagine

dermatomo

Muscolatura Ossa

Tessuti connettivi

Origine dei tessuti degli arti

Epiectoderma

falangi carpo

metacarpo

scapola

preaxial border

postaxial border

SHH

Becker and Duchenne muscular dystrophy Emery-Dreifuss muscular dystrophy

Facioscapulohumeral muscular dystrophy Limb-girdle muscular dystrophy

Scapuloperoneal muscular dystrophy Congenital muscular dystrophy

Muscular Dystrophy There can be abnormalities associated directly with muscle differentiation and

function as well as those mediated indirectly by abnormalities of innervation

or skeletal development and other associated systems.

Duchenne and Becker types of muscular dystrophy Muscular dystrophies are a group of genetic conditions characterized by progressive muscle weakness and wasting (atrophy). The Duchenne and Becker types of muscular dystrophy are two related conditions that primarily affect skeletal muscles, which are used for movement, and heart (cardiac) muscle. These forms of muscular dystrophy occur almost exclusively in males. X-linked dystrophy large DMD gene encoding cytoskeletal protein termed Dystrophin progressive wasting of muscle

assenza del radio

•Prenatal exposure to environmental factors and congenital limb defects[ "Limb congenital defects afflict approximately 0.6:1000 live births. In addition to genetic factors, prenatal exposure to drugs and environmental toxicants, represents a major contributing factor to limb defects. Examples of well-recognized limb teratogenic agents include thalidomide, warfarin, valproic acid, misoprostol, and phenytoin. While the mechanism by which these agents cause dymorphogenesis is increasingly clear, prediction of the limb teratogenicity of many thousands of as yet uncharacterized environmental factors (pollutants) remains inexact."

Thalidomide might downregulate FGF8 expression.

focomelia

aplasie

polidattilia

agenesia centrale