Development Of Limbs Flashcards
When do the limb buds first appear as small elevations of the ventrolateral body wall
End of fourth week
The upper limb buds are visible by day _ to ), where are the lower limb buds are visible when
262-27
1-2 days later
Each limb bud consists of a mass of mesenchyme covered by ___
Ectoderm
The mesenchyme is derived from the somatic layer of the __ ___
Lateral mesoderm
The limb buds elongate by proliferation of the ___
Mesenchyme
Although the early stages of limb development are alike for the upper and lower limbs, there are distinct differences. Why
Bc of their form and function
The upper limb buds develop opposite the __ ___ segments, whereas the lower limb buds form opposite the ___ and ___ ___ segments
Caudal cervical
Lumbar and upper sacral segments
At the apex of each limb bud, the ectoderm thickens to form an apical ectodermal ridge. What is the AER
Specialized multilayered epithelial structure, interacts with the mesenchyme int he limb bud, promoting outgrowth of the bud for which BMP is essential
Retinoids acid promotes the formation of the limb bud. How
By inhibiting FGF8 signaling
The AER exerts an inductive influence on the limb mesenchyme that initiates growth and development of the limbs in a proximodistal axis
Mesenchymal cells aggregate at the posterior margin of the limb bud to form a zone of polarizing activity
FGF from AER activate what, causing what
The zone of polarizing activity
Causing expression of Shh, which controls the patterning of the limb along tha AP axis
Expression of wnt7 from the dorsal epidermis of the limb bid and engrailed (En-1) fromt he ventral aspect is involved in specifying the dorsoventral axis
The AER itself is maintained by inductive signals from Shh and Wnt7
The mesehchyme adjacent to the AER consists of undifferentiated, rapidly proliferating cells, whereas the mesenchymal cells proximal to it differentiate into blood vessels and cartilage bone models
For cartilage formation, TGFB signaling plays. A key role. The distal ends of the limb buds eventually flatten into hand and foot plates
By the end of the 6th week of development, mesenchymal tissue in the hand plates has condensed to form what
Finger buds-digital rays
What are fingerbuds/digital rays
Outline the pattern of the digits
During the 7th week, similar condensations of mesenchyme in foot plated form what
Toe buds/digital rays
At the tip of each digital ray, a part of the __ induced development of the mesenchyme into the mesenchymal primordia of the bones in the digits
AER
The intervals between the digital rays are occupied by ___ ___
Loose mesenchyme
Soon the intervening regions of mesenchyme undergo ____ forming notches between the digital rays
Apoptosis
As epoptosis occurs, separate digits are produced by the end of the __ week
8th
What controls the cell apoptosis between digits
Anatagonism between TGFB and retinoids acid
What happens if you block cellular and molecular events during the apoptosis between digits
Webbing, fusion of the fingers or toes
Syndactylyl
Webbing, fusion of fingers or toes
The mesenchyme in a limb bud gives rise to what
Bones, ligaments, and blood vessels
As the limb bud elongate during the early part of the 5th week, mesenchymal models of the bones are formed by cellular aggregations
Ok
___ __ appear later in the fifth week
Chondrification centers
By the end of the sixth week, the entire limb skeleton is cartilaginous
Ok
Osteogenesis of th elong bones begins in the _ week from primary ossification centers in the diaphysis of the long bones
Diaphyses
Ossification centers are present in all long bones by the _ week
12th
Primary ossification of the carpal bones begins during the _ year
1st
From the dermomyotome regions of the somites, myogenic precursor cells also migrate into the limb bud and later differentiate into ___,
Myoblasts
As the long bones form, myoblasts aggregate and form a large muscle mass in each limb bud.
In general this muscle mass separated into dorsal (extensor ) and ventral (flexor) components
The muscle mass separates into __(extensor) and __(flexor)
Dorsal
Ventral
Early in the 7th week, the limbs extend centrally and the preaxial and postaxial borders are cranial and caudal,
Respectively
The upper limbs rotate __ through 90 degrees on their longitudinal aces
Laterally
The future elbows point ___ and the extensor muscles lie on the lateral and posterior aspects of the limb
Dorsally
The lower limbs rotate __ through almost 90 degrees
Medially
The future knees face __ and the extensor muscles lie on the __ aspect of the lower limb
Ventrally
Anterior
Motor axons arising from the spinal cord enter the limb bud during the _ week and grow into the dorsal and ventral muscle masses
Fifth
Sensory axons enter the limb buds after the motor axons and use them for guidance
True
__ _ __, the precursors of Schwann cells, surround the motor and sensory nerve fibers into e limbs and form the neurolemmal myelin sheaths
Neural crest cells
What is a dermatome
Area of skin supplied by a single spinal nerve and its spinal gangl
During the _ week, the peripheral nerves grow from the developing limb plexuses into the mesenchyme of the limb buds
5th
The spinal nerves are distributed in segmental bands, suppplying both the dorsal and ventral surfaces of the limb buds.
As the limbs elongate, the cutaneous distribution of the spinal nerves migrates along the limbs an no longer reaches the surface in the distal part of the limbs
Although the original dermatome pattern changes during growth of the limbs, an orderly sequence of distribution can still be recognize din the adult
Ok
In the upper limb, the areas supplied by _ and _ adjoin the areas supplied by _ - and _, but overlap between them is minimal at the ventral axial line
C5 and c6
T2, T1, and C8
Bc there is overlapping of dermatomes, a particular area of skin is not exclusively innervated by a single segmental nerve
The limb dermatomes may be treated progressively down the lateral aspect of the upper limb and back up its medial aspect
The limb buds are supplied by branches of the __ arteries
Intersegmental
The intersegmental arteries arise from the dorsal aorta and from a fine capillary network throughout the ___
Mesenchyme
The primordial vascular pattern consists of a primary axial artery and its branches which drain into a peripheral marginal sinus
Blood int he sinus drains into a peripheral vein
The vascular pattern changes as the limbs develop, chiefly as a result of vessels sprouting fro existing vessels (angiogenesis)
The new vessels coalesce with other sprouts to form new vessels
The primary axial artery becomes the brachial artery in the arm and the ulnar and radial arteries in the forearm, its terminal branches of the brachial artery
As the digits form, the marginal sinus breaks up and the final venous pattern, represented by the basilica and cephalic veins and their tributaries develops
In the thigh the primary axial artery is represented by the deep artery of the thigh
In the leg, the primary axial artery is represented by the anterior and posterior tibial arteries
Ectrodactylyl
Cleft hand or cleft foot where one or more central digits are absent
What causes ectrodactylyl
Failure of one or more digital rays to develop
So hand or foot is divided into two parts that oppose each other
Syndactyly
Remaining digits are partially or completely fused
Congenital absence of radius
Radius is partially or completely absent. Hand deviates laterally (radially) and the ulna bows with the concavity on the lateral side of the forearm.
What causes congenital absence of the radius
Failure of the mesenchymal primordium of the radius to form during the 5th week
Or genetic factors
Polydactylyl
Supernumerary digits
Common
Usually incompletely formed and lacks proper muscular development , rendering it uselesss
Are extra digits medial or lateral on hand and feet
Medial or lateral hand
Usually lateral foot
Polydactylyl is inherited how
AD
What is the most common limb defect
Cutaneous syndactylyl
What is cutaneous syndactylyl
Simple webbing of digits
Is cutaneous syndactylyl more common in hand or foot
Foot
Syndactylyl is most frequently observed between _ and _ fingers, and between te _ and _ toes
3,4
2,3
How is cutaneous syndactylyl inherited
Simple dominant or simple recessive.
What causes cutaneous syndactylyl
Failure of the webs to degenerate between two or more digits
In some cases of syndactylyl there is synostosis. What is synostosis
Fusion of bones
Osseous syndactylyl
When the notches between the digital rays do not develop during the seventh week as a result of separation of the digits does not occur
Arthrogryposis muliplex congenita
Heterogenous group of MSK disorders characterized by multiple contracture, and immobility of two or more joints from birth
Incidence of arthrogryposis multiplex congenita
1/300
More males in sex linked cases
Cause of arthrogryposis multiplex congenita
Neurologic (central and peripheral nervous system defects
Non-neurologic (cartilaginous defects and restricted movement in utero)
Congenital talipes
1/1000
Talipes equinovarus
Most common
Males
Sole of foot is turned medially and the foot is inverted
Cause of talipes
Hereditary
Environmental
Follows multifactorial pattern of inheritance :intrauterine position that results in abnormal positioning of the feet may cause talipes if the fetus is genetically predisposed to this deformity
Amelia
Complete absence of limb
Meromelia: hemimelia
Partial absence of a limb
Meromelia:phocomelia
Hands and feet are attached close to the body
Suppression of limb bud development in early part of fourth week
Amelia
Arrest or disturbance of the differentiation or growth of the limbs during the 5th week results in what
Meromelia
HOW, BMP, SHH, WNT7, EN1, others
Brachydactylyl or osteogenesis imperfecta
MUTANT GENES
Thelidomide
Teratogen
Combination of genetic and env factors
Congenital dislocation of the hip
Vascular disruption and ischemia
Limb reduction defects
