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Flashcards in Embryology Deck (59):

Limb buds

- Start to develop during the later part of the 4th week
- Development begins as soon as the TRILAMINAR embryo completes its LATERAL folding
- There is one pair of upper limbs and one pair of lower limbs at this point

REMEMBER: at week 4 there are 4 limbs


Upper limb buds

- Appear as two elevations on each side of the body
- Can be seen by day 26-27 at the inferior segment of the developing cervical region (C5-T1)


Lower limb buds

- Appear first as two elevations from the inferior part of the ventrolateral segment of the embryo (L2-S2)
- Note that the lower limbs originate from a slightly larger segment than the upper limb buds
- Development of teh lower limb buds lags about 2 days behind the upper limb buds


Explain why the lower limb bud development lags behind the upper limb bud development

- This follows the normal pattern of cranial to caudal development
- Cranial structures always appear first


Both upper and lower limb buds

- Originally contain a core of mesenchymal cells that are derived from teh somatic component of the lateral mesoderm layer of the embryo
- Further development and enlargement of the limb buds initially begins by a very fast division of the mesenchymal cells


Cell division at the limb buds is under the direct control of which gene?

HOX (homebox-containing) gene

NOTE: HOX is important for the development of individual bones of the limb***


What is the apical ectodermal ridge (AER)?

- The proliferating mesenchymate at the site of limb development is covered externally by cells of the ectoderm layer (similar to other parts of the body)
- A the distal segment of the limb bud (apex), the ectodermal cells undergo proliferation
- There is considerable thickening at the apex, which is known as the apical ectodermal ridge (AER)

REMEMBER: it tells you where it is located and what it is made of - apical ectodermal ridge


Role of AER

- AER is unique in that it controls the future development of the limb
- Initiates growth in a proximal to distal direction
- Limbs do NOT develop in the absence of AER
- Transplantation of this ridge induces limb development at that location

AER is important in LENGTHENING the limb***


What allows for the ability of AER to induce growth?

- The ability of AER to induce growth is a result of the expression of fibroblast growth center



Development of hands and feet

- The HOX gene controls the "patterning" of the limbs
- The distal ends of the limb buds flatten out into paddle-like hands and feet


What happens to the hand by week 6?

The hand paddles show digital rays (eventual fingers)


What happens to the foot by week 7?

During the early part of the 7th week, toe rays can be seen (eventual toes)


Describe the growth and development of digits

- Initially digits are attached to each other by loose connective tissue
- Separation of the individual digits takes place during the 8th week by apoptosis in mesenchymal tissue between digits


What if apoptosis is interrupted/fails?

If apoptosis is interrupted or doesn't happen, syndactyly will result (attached fingers)


What happens if extra digital rays develop?

- Occasionally additional rays develop in the hand or foot, leading to polydactyly (extra digits)
- The extra digits are usually smaller in size than regular digits


What part of the mesenchyme of limb buds does the HOX gene control development of?

- Bones
- Joints
- Cartilage
- Fascial layers
- Blood vessels
- Lymphatic vessels


Describe skeleton development

- The entire skeleton of the limbs at one time consists of cartilage models of bone
- The cells for this cartilage are derived from the original mesenchymal cells of the embryo


Describe the timing of skeleton development

- This development begins during the 5th week and by the 6th week, the entire cartilaginous skeleton is complete
- During the 7th week, the cartilaginous bone model starts to undergo endochondral ossification


Describe endochondral ossification

- Chondrocytes are replaced by bone-producing cells
- Endochondral bone formation begins in the diaphysis of long bones (i.e. phalanx, metatarsals) because they are the primary centers of ossification


Describe secondary centers of ossification

- Long bones also develop secondary centers of ossification in the epiphysisi
- Each long bone has a primary and a secondary ossification center


Migrant cells

- The developing limbs get "migrant cells" from other locations in the developing embryo in addition to the original mesenchymal cells they develop from


What type of migrant cells do the developing limbs get?

- Myogenic cells
- Dermatomal cells
- Axonal processes
- Neural crest cells


Myogenic migrant cells

- Originate from the dermomyotome region of the somites
- They then migrate into the mesenchymal cells of the limb buds
- They eventually differentiate into myoblasts
- These myoblasts give rise to muscle cells of the limbs
- There are cervical and lumbosacral myotomes


Cervical myotomes

Give rise to pectoral girdle muscles


Lumbosacral myotomes

Provide precursor cells for the pelvic girdle


Dermatomal cells

- These cells are derived from somites
- Provide cells that stay deep to the ectoderm
- Dermatoma cells give rise to the dermis of the skin


Axonal processes

- These cells migrate from the spinal cord to become the nerves of the limbs


Neural crest cells

- Schwann cells (supporting cells of the nervous system) are derived from neural crest cells
- Mesenchymal cells of the limbs organize the neural crest cells once they arrive and control their expression in the limbs


Describe the position of the embryo before rotation

- Both the upper and lower limb buds protrude anteriorly from the body
- They extend from he trunk so that the longitudinal axis of the limb bud (axial line) is at 90 degrees to the long axis of the trunk


Preaxial region

- The are of the limb superior (cranial) to the axial line is called the preaxial region
- The superior border of the preaxial compartment is the preaxial border
- The preaxial border is along the same line as the thumb or great toe

NOTE: think of the "thumbs up" to remember the thumb is on the superior side


Postaxial region

- The area of the limb inferior (caudal) to the axial line is called the postaxial region
- The inferior border of the postaxial compartment is the postaxial border
- The postaxial border is along the same line as the 5th toe or little finger


Muscle masses before rotation

- Muscle masses of the limbs can also be divided into preaxial and postaxial muscles based on their location
- Preaxial compartment (superior) contains flexor muscles
- Postaxial compartment (inferior) contains extensor muscles


Rotation of the limbs

- Limb rotation occurs during the early part of the 7th week
- Limbs rotate along the long axis, changing the orientation of the compartments and the structures within those compartments
- Both sets of limbs go through a 90 degree rotation, but they occur in opposite directions


Upper limb rotation

Rotate in the lateral direction
- Think of the "thumbs up" going out laterally to the anatomical position


Lower limb rotation

Rotate in the medial direction
- Think of the feet being point out laterally by 90 degrees and coming in to the anatomical position


Impact of limb rotation direction

Because the upper and lower limbs rotate in opposite directions, the pre- and post-axial compartments no longer correspond with each other


Upper limb muscle compartments

- Flexor compartment of upper limb (pre-axial) now faces anteriorly (anatomical position)
- Extensor compartment of upper limb (post-axial) now faces posteriorly


Lower limb muscle compartments

- Flexor compartment of the lower limbs (pre-axial) now face posteriorly to plantarflex the foot
- Extensor compartment of the lower limb (post-axial) now faces anteriorly to dorsiflex the foot


Differences due to opposite limb rotation

- This explains why the two homologous bones (tibia and radius) are located on the opposite side of the limbs and why the thumb is located laterally and the great toe is located medially
- The knee and elbow (two homologous joints) also face opposite directions


Frequency of limb defects

2/1000 births


Drug linked to birth defects in the 1960s

- In the early 60s there was a high incidence of limb defects, which was traced back to a drug known as thalidomide, which was used to treat morning sickness in pregnant women
- The most susceptible time for producing limb defects was found to be between day 24-36
- This is known as the critical period


Primary axial artery

- The initial lower limb blood supply comes from teh primary axial artery ("axis artery")
- This eventually disappears and is replaced by the external iliac branches


Failure of primary axial artery to form

- Failure of the axial artery to form is linked to lack of blood to developing limbs and therefore BIRTH DEFECTS



Extra digits which results from having extra digital rays during development



Attached digits with results from a lack of apoptosis (programmed cell death)



Absence of limbs



Absence of a part of the limb


Cleft foot (or hand)

AKA "lobster claw deformity"
- Results from a failure of development of one or more digital rays
- The hand and foot appear to be split down the middle



Short digits
- Brady = short


Congenital club foot

This defect applies to any abnormality of the foot involving the talus
- It is more common than some of the other defects (1/1000)
- The affected individual walks on teh ankle rather than the foot
- The sole of the foot is usually turned medially and the foot is inverted


Summary of key points...



Critical period

24-36 days post-fertilization


End of week 4

The limb bud consists of mesenchyme surrounded by ectoderm


AER and HOX genes

Promote limb growth in a proximal to distal manner


Week 7

Digital rays appear


Week 8

Digits separate by apoptosis


Bone development

Bones form from mesenchymal precursors around week 5 and follow endochondral ossification beginning at week 7


Muscle development

Muscles form from myogenic cells which are organized as myotomes and by extensor/flexor compartments



Follow myotome organization and relate to medial 90 degree rotation of lower limb