Sviluppo dello scheletro - Homepage | DidatticaWEB
Transcript of Sviluppo dello scheletro - Homepage | DidatticaWEB
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Svi
lupp
o sc
hele
tro
e m
usco
li
(app
arat
o m
usco
lo-s
chel
etr
ico)
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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
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• 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:
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sclerotomo
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Mesenchima dal:
• Mesoderma laterale somatico
(ossa degli arti e dei cinti scapolare e pelvico)
Scheletro appendicolare
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RA
M M
M
CEA
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OSSIFICAZIONE
• Ossificazione diretta o membranosa
• Ossificazione indiretta
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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
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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
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frontalee
parietal
temporale
mandibola
mascella
grande ala sfenoide
nasale
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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
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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)
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occipitale
temporale
condrocranio
Temporale (parte timpanica e petrosa)
sfenoide occipitale (squama)
osso ioide
etmoide vomere
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The sternum develops from the somatic mesoderm in the ventral body wall.
Le costole originano dai processi costali delle vertebre toraciche
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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
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Embrione di 36-40 g colorazione alizarina
clavicola
femore
Il primo osso cartilagineo in cui compare un centro di ossificazione I è la clavicola
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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)
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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
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Giantism
Hypopituitarism
Bone tissue diseases
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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
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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
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Difetti nella formazione o nelle funzioni degli osteoclasti portano ad un aumento della massa di tessuto osseo e causano una patologia
chiamata osteopetrosi
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nell’osteopetrosi
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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.
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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
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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
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somitomeri
som
iti
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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
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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
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sclerotomo
IGF
Epiectoderma
PAX1
PAX1
SHH
MRF4
MRF4
SIX 1-2 (Sineoculis
homeobox homolog 1-4)
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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
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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.
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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
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Sviluppo degli arti
IV settimana
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• Ro
tazion
e degli arti
8th week
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IV settimana V-VI settimana VII-VIII settimana
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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
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falangi carpo
metacarpo
scapola
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preaxial border
postaxial border
SHH
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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.
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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
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assenza del radio
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•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
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aplasie
polidattilia
agenesia centrale
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