Development of limbs Flashcards by Callum Hill

When does limb development being?

Near the end of the 4th week

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What leads to activation of limb development?

Activation of mesenchymal cells int he somatic lateral mesoderm

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What regulates patterning within limb development?

Homeobox genes regulate patterning

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Which day do the upper Limb buds appear?

Day 24

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When do the lower limb buds appear?

Day 25-26

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What are HOX genes?

Regionally expressed in limbs and determine which skeletal element formed
HOX gene expression results from a combination of the
expression of SHH (Sonic Hedgehog), FGF’s (Fibroblast Growth Factors) and WNT-7a

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Which HOX genes are expressed in upper limb?

HOXd 9-13

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If you removed HOX 11 and HOXd 11 what would occur?

Radius and ulna would not form

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HOX 9?

> Scapula*
> Humerus 
> Radius and ulna 
> Carpals 
> Metacarals and > phalanges

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HOX 10?

> Humerus*
Radius and ulna
Carpals
Metacarals and > phalanges

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HOX 11?

> Radius and ulna*
Carpals
Metacarals and > phalanges

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HOX 12?

> Carpals*

> Metacarals and > phalanges

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HOX 13?

> Metacarals and phalanges*

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How do limb buds occur?

Elongate by the proliferation of mesenchyme

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Upper limb buds develop opposite what?

Caudal cervical segments

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Lower limb buds develop opposite what?

The lumbar and sacral segments

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At the apex of limb bud the ectoderm thickens to form what?

Apical ectodermal ridge (AER)

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Where is the apical ectodermal ridge restricted to?

End of limb bud

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The mesenchyme adjacent to the AER consits of what?

Undifferentiated, rapidly proliferating cells

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whereas mesenchymal cells proximal to it differentiate into what?

Blood vessels and cartilage bone models

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What is the apical ectodermal ridge?

> Thickened section of the ectoderm consisting of a multinucleate epithelial structure

> Exerts an inductive influence on the limb mesenchyme

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What occurs day 32 of development - limb development?

Paddle-like-upper limb bud

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What occurs day 35 of development - limb development?

Handplate formed

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What occurs day 44 (Week 6) of development - limb development?

> Digital rays appear in hand plate
Notch between digital rays, webbed fingers

> Lower limb bud

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What occurs day 48 (Week 7) of development - limb development?

> Upper limbs bend at the elbow > Fingers are slightly short and webbed > Digital rays are formed in the foot plate

What occurs day 58 (Week 8) of development - limb development?

Fingers and toes are distinct and separated

Why is apoptosis important within limb development?

Programmed cell death (apoptosis) is responsible for the tissue breakdown in the interdigital regions –mediated by bone morphogenetic proteins

How are cartilaginous precursors of limb nones developed, when?

Chondrification and by week 6

When do primary centres of ossification appear?

Between weeks 8 and 12 of development

Which type of ossification occurs during limb development?

Endochondrial ossification for all limb bones except the clavicle (membranous)

Which type of ossification occurs during development of the clavicle?

Membranous ossification

What has to happen for the upper limbs to be positioned correctly?

Upper limbs rotate 90o laterally so that extensors are on the lateral and posterior surfaces (and the thumb is lateral)

What has to happen for the lower limbs to be positioned correctly?

Lower limbs rotate 90o medially so that the extensors are on the anterior surface (and the big toe is medial)

Which way do upper limbs rotate during development?

90o laterally

Which way do lower limbs rotate during development?

90o medially

Which week of development do peripheral nerves grow from developing limb plexus?

The 5th week

Limb birth defects - Total absence?

Amelia

Limb birth defects - partial absence?

Meromelia

Limb birth defects, - some long bone absence?

Phocomelia

Limb birth defects - all parts present but small?

Micromelia

Mode of inheritance of lobster claw foot?

Autosomal dominated trait

Critical period of limb development?

14-26 days after fertilisation

What is polydactyly?

Presence of more than 5 digits on the hands or feet

Cause of polydactyly?

Can be either teratogen induced or inherited

Characteristics of extra digit in polydactyly?

Extra digit is incompletely formed and lacks muscular development

What is cutaneous syndactyly?

``` Cutaneous Syndactyly (simple webbing between the digits) is a common limb defect ```

What is osseous syndactyly?

Osseous Syndactyly (fusion of bones) occurs when notches between the digital rays fail to develop

Does syndactyly occur more frequently in the hand or the foot?

The foot

Syndactyly, common or rare?

Common birth defect in the hand or foot

What is thalidomide?

> Used between 1957-1962 was a commonly used sleeping tablet and anti-nauseant > Now used to help cancer, leprosy and AIDs patients

When should thalidomide not be taken?

> During pregnancy particularly within the sensitive period, weeks 4-8 > For this reason we do not give it to woman of child bearing age

How can thalidomide effect development?

> Absence or deformity of long bones > Intestinal atresia > Cardiac anomalies

What is the name for clubfoot?

Talipes equinovarus

What is Talipes equinovarus (club foot)?

The sole of the foot is turned medially and the foot is inverted?

What is cause of Talipes equinovarus (club foot)?

1) Multifactoral (Genetic and environment factors) | 2) Abnormal positioning or restricted movement of the foetus's lower limb in utero - Evidence is inconclusive

Which percentage of infants have congenital dislocation of the hip?

15% of infants

When does congenital dislocation of the hip usually occur?

Common after breeched deliveries

What causes developmental dysplasia of the hip?

Abnormal development of acetabulum

Generalised joint laxity?

> Multifactorial | > Associated with congenital dislocation of the hip

Could label the diagram above and ask to identify the apical ectodermal ridge

Slide 4 of lectures embryology

What is the last step in the development of hands and feet?

Loss of the webs separating the digits of finger and toes

The process of bone formation is known as what?

Ossification

Epiphyseal cartilage form what?

The growth plates

Cartilage to bone is known as what?

Endochondrial ossification

Myofilaments form from what?

Mesochyme tissue = Myoblasts and myotubes | Some are from neurocrest cells

Syndactyly an come up in exam to identify

E.g. Radiograph shows osssous syndactyl

What are Homebox (HOX) genes mainly involved in?

Limb development