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MSS Weeks 3-5 > Spine, Muscle and Limb Development > Flashcards

Spine, Muscle and Limb Development Flashcards

0
Q

What are the precursors for: Smooth muscle Cardiac muscle Skeletal muscle

A

Smooth - Splanchnic mesoderm and local mesenchyme

Cardiac - Splanchnic mesoderm

Skeletal - Paraxial mesoderm

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1
Q

What are the three types of muscle tissue?

A

Smooth Cardiac Skeletal

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2
Q

What is intraembryonic mesoderm divided into?

A

Pariaxial mesoderm

Intermediate mesoderm

Lateral mesoderm

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3
Q

Which mesoderm forms somites?

A

Paraxial mesoderm

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4
Q

What is a somite?

A

Temporary structure in embryo allowing embryo to segregate certain precursor structures that eventually become skeletal muscle and bone

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5
Q

Two types of tissue in the embryo

A

Epithelium and mesenchyme

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6
Q

How does mesenchyme become somite?

A

Mesenchymal to epithelium transformation causes a structure with an outer surface of epithelium and inner portion of mesenchyme

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7
Q

What is the outer epithelial surface of somites called

A

Dermomyotome

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8
Q

What causes differentiation of the dermomyotome

A

Signals from surrounding tissues (notochord, neural tube and BMPs)

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9
Q

What is the lateral somite frontier

A

The boundary between different sets of signals sent to the somite

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10
Q

What is the primaxial domain?

A

Forms muscles that attache to scleratome derived bones (vertebrae)

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11
Q

What is the abaxial domain

A

Forms muscles of ventrolateral abdominal wall and limbs

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12
Q

What do the dermomyotomes form after they are differentiated?

A

Myogenic cells, which then become myoblasts

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13
Q

How is skeletal muscle formed from myoblasts?

A

Signals from other cells cause myoblasts to fuse together into myotubules which then join to form skeletal muscle cells

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14
Q

Why does skeletal muscle have multiple nuclei

A

Because it is formed from multiple myoblasts

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15
Q

The central region of the dermomyotome forms…

A

Satellite cells - precursors to skeletal muscle cells (muscle stem cells)

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16
Q

What are the master regulators for skeletal muscle formation?

A

Myo-D family of genes: Myf-5 Myogenin MRF-4 PAX-3 PAX-7

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17
Q

How do myotubes differentiate into different types of muscles (proposed strategies)?

A

Change in muscle fiber direction (abdominal muscles) Tangential splitting into layers Fusion of adjacent myotomes (for large muscles)

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18
Q

How do skeletal muscles become innervated

A
  • Innervated early as pre-muscle masses - Some pre-muscle masses take their innervation with them as they migrate - Spinal nerves innervate somite derived skeletal muscles of trunk and limbs
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19
Q

What does myotome mean structurally?

A

All of the muscles that come from a single pair of dermomyotomes (which have the same innervation)

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20
Q

What innervates myotomes?

A

Branches of primary Rami of Spinal nerves

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21
Q

What are the muscles innervated by dorsal primary rami?

A

Epaxial muscles (above the axis) - Back muscles

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22
Q

What muscles are innervated by the ventral primary rami?

A

Hypaxial muscles (below the axis) - abdominal muscles

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23
Q

How many weeks does it take for all muscle groups to have formed

A

8 weeks

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24
Q

What is abnormal skeletal muscular development

A

Absence of a muscle or part of a muscle

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25
Q

What is missing in Poland syndrome

A

Pectoralis major

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26
Q

What is missing in Prune Belly syndrome

A

Abdominal muscles

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27
Q

What is congenital toricollis

A

Missing sternocleidomastoid

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28
Q

What is the most common congenital muscle problem?

A

Muscular dystrophy

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29
Q

Myoblasts from the _________ dermomyotome form primaxial domain muscles

A

dorsomedial

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30
Q

Myoblasts from the ___________ dermomyotome form abaxial muscles

A

dorsolateral

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31
Q

What two tissues make up the skeleton?

A

Bone and cartilage

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32
Q

What embryonic progenitor tissues are used to form skeletal tissues?

A

Mesenchyme

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33
Q

In the trunk, mesenchyme is derived from…

A

Paraxial mesoderm

Somatic mesoderm

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34
Q

In the head, mesenchyme is derived from…

A

Neural crest ectomesenchyme Head mesoderm

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35
Q

What is STFM

A

Skeletal Tissue forming mesenchyme

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36
Q

What are some of the shared features of STFM development?

A
  • Often skeletal progenitor cells migrate or are displaced from their site of origin
  • STFM condenses into pre-skeletal condensations
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37
Q

What influences STFM differentiation?

A
  • Epithelial-mesenchymal interactions
  • Specific transcription factors
  • Other signaling molecules
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38
Q

What is the osteoblast-specific transcription faster gene (bone master gene)

A

RUNX2a (CBFA1)

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39
Q

What is the chondroblast specific transcription factor

A

Sox 9

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40
Q

What is the first step in the primary differentiation pathways of STFM?

A

The initial step is a condensation of pre-skeletal mesenchyme (influenced by signals from adjacent epithelium)

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41
Q

What transcription factors are involved in endochondrial ossification?

A

Sox-9 Ihh; VEGF RUNX-2

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42
Q

What transcription factor is involved in intramembranous ossification?

A

Runx-2

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43
Q

What is the ossification center?

A

The area of bone where ossification begins

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44
Q

Where are locations for the primary center of ossification?

A

The initial center to appear

  • Shaft of long bone
  • Center of flat bone

First appears at 7 weeks of development

45
Q

When would you see secondary ossification centers?

Where would you see secondary ossification center?

A

Appear in perinatal, postnatal or postpuberal period Ends of long bones (epiphysis), heads of ribs

46
Q

When does the secondary ossification center close?

A

20s -30s and controlled by hormones

47
Q

Why are there spaces between the long bones of the limbs as seen on the X-ray of a newborn?

A

Those spaces are still cartilage

48
Q

What is Bone Age?

A

The amount of Epiphyseal cartilage retained - Comparison of bone and chronological ages is a measure of skeletal growth and maturation

49
Q

Generalized Skeletal Tissue Dysplasias

A

May affect all or part of the skeleton:

  • Often affect growth and may result in short or tall stature
  • Often a component of the ECM, causing it to be defective
  • Often there is a recognized genetic component
50
Q

Marfan’s syndrome

A

Alteration of Fibrillin production

51
Q

Mucopolysaccharidoses

A

Defect in synthesis, storage and transport of a particular lysosomal enzyme - results in accumulation of substrate (lysosomal storage diseases)

52
Q

Altered hormone secretion can affect skeletal growth. What happens in

Growth Hormone (Increases)

Growth Hormone (Decreases)

Thyroid Hormone (Decreases

A

Growth hormone Increased: Lead to Gigantism

Growth Hormone Decrease: Lead to Pituitary Infantilism (Dwarfism)

Thyroid hormone Decrease: Lead to Cretinism (mental deficits included)

53
Q

Which disease results from a mutation in the gene encoding fibroblast growth factor receptor 3 (FGFR3)?

A

Achondroplasia

54
Q

What is the abnormality seen in achondroplasia?

A

Failure of endochondral ossification

55
Q

What lower extremity deformity is seen in achondroplasia?

A

Genu varum (bowlegs)

56
Q

What cell functions abnormally in osteopetrosis?

A

Osteoclasts

57
Q

How would you treat osteopetrosis?

A

Bone marrow transplant

58
Q

What are the two parts of a skeleton?

A

Axial and appendicular

59
Q

What’s the genetic abnormality in osteogenesis imperfecta?

A

Type 1 collagen

60
Q

What types of bones are formed by:

  • Paraxial mesoderm
  • Somatic mesoderm
A

Paraxial mesoderm: vertebral column and ribs Somatic mesoderm: sternum and limb skeleton

61
Q

Which signal causes the medial and inferior portions of the somite to become mesenchymal cells?

A

Sonic the hedgehog

62
Q

What is the scleratome?

A

Precursor to the vertebrae formed from portions of the somites

63
Q

Scleratome tissue organizes into _____ and _______ subdivisions

A

Cranial; caudal

64
Q

What is resegmentation of Scleratome tissue?

A

The process by which the two subdivisions of the scleratome separate from each other due to the spinal nerve cutting across them

  • The cranial portion of one scleratome fuses with the caudal portion of an adjacent scleratome
  • Myotome does not separate with the scleratome and ends up linking pairs of vertebrae
65
Q

Subdomains of scleratome tissue:

Central:

Ventral:

Dorsal:

Lateral:

Somitocoel cells:

A

Central: Pedicle, proximal ribs

Ventral: Vertebral body, IV disc

Dorsal: Dorsal part of neural arch, spine

Lateral: Distal rib

Somitocoel cells: Vertebral joints, IV disc, proximal ribs

66
Q

Cells from the cranial half of the scleratome contribute to:

A

Vertebral body, small parts of neural arch and distal rib (in thoracic region

67
Q

Cells from the caudal half of the scleratome contribute to:

A

Vertebral body, transverse process, most of neural arch and proximal part and main part of distal rib (in thoracic region)

68
Q

Cells at intersegmental boundary and somatocoel cells (of the scleratome) form:

A

The intervertebral disc

69
Q

Patterning of vertebrae is determined by:

A

Homeobox genes (Hox genes)

70
Q

What happens to the costal process in the thoracic region?

A

Extends laterally and becomes a rib

71
Q

Closure of the neurocentral junction (primary growth center of vertebrae) occurs at what age?

A

3 - 6 years old

72
Q

What is the klippel-fiel sequence?

A

Fusion of cervical vertebrae

  • Number of cervical bodies is less than normal.
73
Q

Dysraphism

A

Open Vetebral Column

Due to failure of fusion of the Nueral arches of the A SINGLE vertebra process.

74
Q

Rachischisis

A

Many or all vertebrae have unfused spinous processes

Extensive opening of vertebral column with CNS involvement

75
Q

Spina Bifida

A

Variation in length of opening of vertebral column

  • lack of formation of spinous processes
  • Only a few vertibrae are unfused
76
Q

Defects Resulting in assymetry

A

Congenital kyphosis

Congenital lordosis

Congenital scoliosis

77
Q

Two causes of congenital scoliosis

A

Failure of segmentation

Failure of formation

78
Q

Describe the formation of the sternum

A

Sternal bands fuse together to form cartilage sternum; ossification centers lead to an ossified sternum

  • Sternum is the location of the first ossification centers in development
79
Q

Abnormal development of ribs can lead to…

A
  • Extra ribs
  • Abnormal ribs (fused or forked)
  • Clefts
  • Pectus Excavatum (hollow)
  • Pectus carinatum (keel shaped)
80
Q

What is the basic organizational plan of tissues in the adult limb?

A

Consist of:

  • Skeletal elements
  • Skeletal muscles
  • Fibrous connective tissue
  • Neurovascular Structures
  • Skin
81
Q

Limb Precursor tissues

A

Limb mesenchyme (somatic mesoderm and somitic mesoderm)

Surface ectoderm

82
Q

Development of the upper limb is ahead of that in the lower limb by about __ - __ days

A

1-2

83
Q

Step 1 of the limb development

A

Establishment of the limb field

  • Bilateral areas of somatic mesoderm induced by gene expression
84
Q

What is the area between the limb fields called?

A

Flank region

85
Q

Step 2 of Limb development

A

Budding (appearance)

  • Located at specific axial levels
  • Budding is an inherent property of mesoderm
86
Q

What is the name of the thickening that appears at the dorsal/ventral surface interface?

A

Apical Ectodermal Ridge (AER)

87
Q

Step 3 of limb development

A

Elongation of the limb

  • Segments appear along a proximal-distal axis
  • Elongation results from epithelial-mesenchymal intearactions at AER/mesoderm interaface
88
Q

Step 4 of limb development (week 5)

A

Tissue formation and organization

  • Differentiation occurs in proximal-distal direciton
  • Somatic mesoderm condenses to form cartilage
  • Somite derived myoblasts migrate into limb to form skeletal muscles
  • Nerves and vascular precursors migrate into limb
89
Q

What are the three linear axes upon which limb development occurs?

A

Proximal-Distal: Elongation, segment formation

Anterior-Posterior: Cranial-caudal/Preaxial-postaxial borders, digit development

Dorsal-Ventral: Compartments - muscles and neurovascular structures

90
Q

What allows a bud to become a 3 part limb?

A

Reciprocal signaling

  • Mesenchyme produces Fgf10 which goes to ectoderm which responds by producing Fgf8 (Fgf8 produces the AER)
  • Retinoic acid - stronger proximally and weaker distally
  • Fgf and Wnt - stronger distally and weaker proximally
91
Q

Role of Mesenchyme in limb development

A

Induces the AER (Fgf10)

Sustains AER (Fgf10)

Determines limb type (upper or lower)

92
Q

AER role in limb development

A
  • Maintains a proliferating pool of mesenchyme cells for linear growth (Fgf8)
  • Maintains A-P axis signaling center
  • Interacts with P-D and A-P specific proteins to provide mesenchyme cells with positional information
93
Q

What is the fate of the mesenchyme adjacent to the AER?

A

Forms segment specific skeletal elements Forms fibrous connective tissue

94
Q

Removal of the AER leads to…

A

Limb truncation - elongation of the limb stops

95
Q

How common are limb malformations?

A

2/1000 births (1/500)

96
Q

Types of limb anomalies (7)

A

Failure of formation of parts

Failure of differentiation

Duplication of parts

Overgrowth of parts

Undergrowth of parts

Congenital Constrictive Band syndrome

Generalized skeletal abnormalities

97
Q

Failure of communication between AER and mesenchyme can lead to…

A

Failure of formation of parts

98
Q

What is a fibular hemimelia

A

Congenital absence of the fibula

  • most common congenital absence of long bone extremities
99
Q

What is Phocomelia? What drug can cause it?

A

Distal part of the extremities are attached directly to the body;

Thalidomide

100
Q

What develops along the anterior-posterior axis in limb development?

A

Digits

101
Q

What is the zone of polarizing activity (ZPA)?

A

A signaling center along the posterior border of the limb that controls pattern of digits

  • mediated by Sonic Hedgehog (Shh)
  • Retinoic acid mimics Shh
102
Q

What happens if an additional ZPA signal is added?

A

Secondary focus of Hox gene expression - duplication of the digits

103
Q

How does apoptosis play a role in limb development?

A

Separation of digits

Absence of distal phalanx of large digit

104
Q

Failure of differentiation leads to…

A

Syndactyly - Two partially combined toes

Sirenomelia - Combined legs

Triphalyngeal Thumb - Three phalanges in the thumb

105
Q

What type of inheritance is involved in duplication of digits?

A

Autosomal dominant

106
Q

Mediators of Dorsal-Ventral patterning

A

Secreted factors: Wnt 7a

Transcription factor engrailed (En)

107
Q

In the anatomical position the thumb is…

A

Cranial

108
Q

What is developmental dysplasia of the hip?

A

Underdevelopment of femoral head or hip socket and general joint laxity

More common in females

109
Q

Cleidocranial Dysplasia

A

Missing clavicle and facial anomalies

110
Q

What is talipes equinovarus?

A

Club foot - turning in of the feet

MSS Weeks 3-5 (22 decks)

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