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Musculoskeletal Block > Embryology > Flashcards

Embryology Flashcards

1
Q

Meromelia vs. Amelia

A

Meromelia: partial absence of limb due to inactivation of AER too early; phocomelia = no true long bones and flipper-like limbs

Amelia: complete absence of limb; inadequate limb mesenchyme with epithelium intact

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2
Q

Weeks 0-2

A
  1. Zygote
  2. Morula
  3. Blastocyst
  4. Embyroblast
  5. Inner cell mass
  6. Bilaminar disc: epiblast and hypoblast
  7. Trilaminar disc: cells invade called the primitive streak and form the ectoderm, mesoderm, and endoderm
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3
Q

Weeks 3-8 and Months 3-9

A

Weeks 3-8: All major organ systems develop

Months 3-9: Growth and Functional Maturation

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4
Q

Ectoderm

A

Epidermis of Skin

Neural Crest: sensory axons, spinal ganglion, melanocytes, and Schwann cells

Neural Tube: CNS and PNS

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5
Q

Mesoderm Differentiation

A
  1. Paraxial - medial; somitomeres (7 pairs) and somites (4 occipital pairs), which contribute to head development; cervicalcoccygeal have 33 pairs for postcranial development
  2. Intermediate - no contributions to limbs
  3. Lateral plate - lateral; splanchnic and somatic mesoderm; limb mesenchyme to make CT, appendicular skeleton, and vasculature
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6
Q

Somite Differentiation

A

Dermatome, Sclerotome, and Myotome

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7
Q

Embryonic Development: Weeks 4-8

A

week 4: limb bud formation; initiate vascular and nervous supply – including formation and completion of neural tube

week 6: paddle-shaped hand- and footplates; hyaline cartilage models form

week 7: limb rotation; muscle masses form

week 7-8: begin ossification process

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8
Q

Outgrowth of Limb Buds

A

upper limb buds (~day 24)
opposite lower 4 cervical & upper thoracic somites; C5-T2

lower limb buds (~day 28)
opposite lower 4 lumbar & upper 3 sacral somites; L2-S2

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9
Q

HOX Genes

A

location of limb buds – determined by homeobox (HOX) genes expression along the embryo

type/shape of limb bones – regulated by HOX genes along the proximodistal axis of the developing limb*

*HOX gene expression (determined by the combinatorial expression of (SHH, FGFs, and Wnt7a) occurs in phases in 3 places

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10
Q

Growth of Limb Regulation

A

Growth of limb - regulated by transcription factors and signaling molecules

Once positioning along the craniocaudal axis is determined (HOX genes), growth must be regulated along proximodistal, A-P, and D-V axes.

Limb outgrowth, which occurs first, is initiated by growth factors (FGF and TBX) secreted from lateral plate/somatic mesoderm.

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11
Q

Outgrowth of Limbs

A
  1. Ectodermal Cap

2. Mesenchymal core - (lateral plate mesoderm) secretes growth factors (FGF & TBX) which initiate outgrowth

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12
Q

Formation of AER

A

Apical Ectodermal Ridge (AER)

Once outgrowth is initiated, BMPs expressed in ventral ectoderm induce the formation of the AER via homeobox gene MSX2
Radical fringe in dorsal ectoderm restricts location of AER to distal tip of limb because AER causes cells to rapidly divide without differentiating called the progress zone. If the AER is not restricted, then cells would not differentiate properly proximodistally

SER separates cells that express radical fringe from those that are not; SER is close to AER

After the AER is established, it expresses FGF-4 and FGF-8 which maintain the Progress Zone (PZ)

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13
Q

Progress Zone

A

Maintained by the AER by secreting FGF
Cells that are rapidly dividing and not differentiating

Cells that leave the PZ differentiate:
Early mesoderm differentiation – proximal limb segment
Late mesoderm differentiation – distal limb segment
Most differentiated cells = zone of polarizing activity (ZPA)

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14
Q

SHH

A

FGF from AER induces SHH expression at ZPA via production of retinoic acid/ vitamin A

Wnt7a maintains SHH in ZPA to cause correct positioning of digits

SHH diffuses through the mesoderm creating a concentration gradient

Maintenance and propagation of SHH expression requires AER-FGF signaling as part of a positive epithelial–mesenchymal feedback loop between the ZPA and the AER

BMP-dependent downregulation of SHH is achieved by inhibiting FGF and Wnt signaling activities that usually maintain SHH expression

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15
Q

Polydactyly

A

occurs if two zones of polarizing activity (ZPA) or when ZPA is interrupted

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16
Q

Dorsoventral Axis Regulation

A

regulated by signaling molecules produced by ectoderm

Dorsal ectoderm – Wnt7a induces expression of Lmx1
Ventral ectoderm – BMPs induce expression of En1
(En1 represses Wnt7a expression restricting it to dorsal)

17
Q

Establishing Axial Polarity

A

Proximodistal: controlled by AER secreting FGF

Pre/post axial (anteroposterior): controlled by ZPA producing retinoic acid that initiates SHH

Dorsoventral : regulated by Wnt7a (also maintains SHH) → LMX1 and BMPs → En1; signaling centers located in dorsal and ventral ectoderms

18
Q

Development of Peripheral Vasculature

A 
Initially: fine capillary network = marginal sinus (beneath AER) – venous outflow
some channels preferentially enlarge, form large central artery  
pattern changes constantly by outgrowth, regression, coalescence.
venous system (low pressure) more variable
19
Q

Development of Joints

A

cell death and matrix changes in zones within cartilaginous rods
early joint development is independent of muscular activity
joint capsule, ligaments, & tendons from mesenchymal condensations

20
Q

Development of Musculature

A

Paraxial mesoderm → somites → myotomes:

Epimere: intrinsic muscles of the back innervated by dorsal primary rami (deep muscles of back)

Hypomere: contribute to rest of muscles and superficial back too

21
Q

Hypomere

A

Hypomere: contributes to muscles of extremities and then split up to dorsal and ventral aspects

Dorsal in the upper limb would be the pronators and supinators and the lower limb is adductors and abductors

22
Q

Innervation of Limbs

A

All limbs are associated with ventral primary rami innervation

dorsal muscle mass innervated by dorsal (posterior) brs. of ventral rami of spinal nn.

ventral muscle mass innervated by ventral (anterior) brs. of ventral rami of spinal nn.

Arms: brachial plexus C5-T1
Legs: lumbosacral plexus L2-S2

23
Q

Limb Rotation

A

Arms: rotate laterally to put extensors on the posterior aspect; coronal to parasagittal orientation

Legs: rotate medially to put extensors on the anterior aspect

24
Q

Interdigital Space Formation

A

Digital rays appear, AER breaks up, leaving intact AER segments over digital ray tips (N=5 per hand/foot)

Reduces amount of FGF transmitted to interdigital spaces and cell death occurs

*Apical ectodermal ridge breaks down and FGFs are lost and begin to get programmed cell death to get the interdigital sapec

25
Q

Syndactyly and Triphalangeal Thumb

A

No selected apoptosis with the AER of the hand/foot plate causes:

  1. Dysregulation of interdigital apoptosis = syndactyly
  2. Dysregulation of terminal apoptosis = triphalangeal thumb
26
Q

Ectrodactyly

A

Lose apical ectodermal ridge = lose entire digit = ectrodactyly/cleft hand/cleft foot
Lobster claw deformity

27
Q

HOX Gene Mutation

A

Problems with limb patterning causing:

  1. Synpolydactyly: multiple fused digits
  2. Short digits or fused carpal bones

*Both are HOX 13 mutations

28
Q

Classification of Limb Defects

A
  1. Reduction defects – all or part of a limb is missing arrest of development, failure of differentiation (e.g., meromelia, amelia, phocomelia)
  2. Duplication defects – supernumerary limb elements (e.g., polydactyly)
  3. Dysplasia defects – malformation of the limb
    overgrowth/undergrowth (e.g., macrodactyly, syndactyly, adactyly), focal defects (e.g., amniotic band syndrome),
    general skeletal abnormalities (e.g., osteogenesis imperfecta)
29
Q

Key Factors that cause Anomalies

A

Amount of mesenchyme available

Duration of the AER inductive influence

Presence of a teratogen

Mechanical factors

30
Q

Teratogen vs. Morphogen

A

Teratogen – any agent or factor that induces or ↑ the incidence of a congenital anomaly in a developing embryo (i.e., factors that cause birth defects); weeks 3-8 are the most critical time that can be affected, especially weeks 4 and 5; months 3-9 defects are less severe/non-existent

Morphogen – signaling molecule that acts directly on cells to produce a specific response (i.e., a substance governing the pattern of tissue development - e.g., retinoic acid, FGF, Wnt, SHH)

31
Q

Morphogens Become Teratogens

A

retinoic acid and receptors normally expressed in developing limb

altered synthesis and action:
if inhibited, limb formation halted
if excess, positional information disrupted

potential sources of excess:
excessive vitamin A intake (hypervitaminosis A)
products for treating acne containing isotretinoin (a retinoid or analogue of vitamin A)

32
Q

Methyloxyethanol

A

Methyloxyethanol: extensively used in industry (paints, textile dyes, printing inks, brake fluid, semiconductor manufacture)

Regression of AER (due to reduced laminin content in the basal lamina of ectodermal cells) causing syndactyly (primarily upper limb)

33
Q

Cadmium

A

Cadmium: extensively used in industry & agriculture; ubiquitous environmental pollutant

Damages DNA in embryonic cells causing limb deformities (syndactyly, polydactyly, hypertrophy)

34
Q

Amniotic Band Syndrome

A

bands of amnion (inner lining of amniotic sac) or adhesions attach to fetus reduces local blood supply

causes abnormal development (including ring constrictions, and amputations)

Connective tissue strands from adhesions or breaks lose and then constrictions around the baby occurs = causes constrictions or amputations

35
Q

Clubfoot (Talipes Equinovarus)

A

Plantarflexed, inverted, deformed talus, observed mainly in ♂

Likely etiology: abnormally low amniotic fluid (oligohydramnios) leading to mechanical pressure of uterine wall on fetus

Abnormal positioning of the legs in utero

Hereditary

Musculoskeletal Block (29 decks)

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