ANATOMICAL POSITION

1. Standing
2. Head facing forward
3. Upper extremity hanging by side, palm of hand facing
forward
4. Lower limbs together with toes pointing forward
 ANATOMICAL PLANES

MEDIAN/MEDIAN SAGITTAL PLANE

Imaginary vertical plane passing longitudinally through the

body from front to back, dividing it into right and left halves.

PARASAGITTAL PLANES
Imaginary vertical plane passing through the body parallel to
the median plane.
CORONAL PLANES (Frontal)

Imaginary vertical plane passing through the body at right

angles to the median plane, dividing the body into anterior and
posterior portions.
HORIZONTAL PLANES (Transverse)
Imaginary planes passing through the body at right angles to both the
median and coronal planes (parallel to the horizon).
 COMMONLY USED TERMS OF RELATIONSHIP AND COMPARISON

ANTERIOR (VENTRAL) Nearer to the front

POSTERIOR (DORSAL) Nearer to the back
MEDIAL Nearer to the median plane
LATERAL Farther from the median plane
SUPERIOR (CRANIAL) Nearer to the head
INFERIOR (CAUDAL) Nearer to the feet
PROXIMAL Nearer to the trunk or point of origin
DISTAL Farther from the trunk or point of origin
SUPERFICIAL Nearer to or on the surface
DEEP Farther from the surface
CENTRAL Nearer to the center
PERIPHERAL Farther away from the center
MOVEMENTS OF THE SHOULDER

Scapula
MOVEMENTS AT THE SHOULDER

Glenohumeral Joint
(Shoulder Joint)
MOVEMENTS AT THE ELBOW

Elbow Joint
 MOVEMENTS AT THE ELBOW

Radioulnar Joint

Forearm
MOVEMENTS AT THE WRIST

Wrist Joint
MOVEMENTS AT THE FINGERS
 MUSCULOSKELETAL DEVELOPMENT
Mesoderm/Ectoderm Interaction

Epithelium

Mesenchyme
OSTEOGENESIS SKELETAL DEVELOPMENT
 AXIAL SKELETON
PARAXIAL MESODERM AND DEVELOPING SOMITES
SCLERATOME
Recall that paraxial mesoderm differentiates
into the dermatome, myotome, and scleratome.

Somitomeres 44 pairs of which 37 form somites.

First 7 pair do not form somites.

Somites (paired) give rise to axial skeleton.

1-4:occipital part of skull, bones of nose, eye, inner ear.

5-12: cervical region
13-24: thoracic region
25-29: lumbar region
30-34: sacral region
35-37: coccygeal region
 OSTEOGENESIS

Intramembranous Ossification membranous sheath develops

in the mesenchyme.

Endochondrial (Intracartilaginous) chondrocytes develop

cartilage matrix.
 OSTEOGENESIS OF AXIAL SKELETAL
DERIVED FROM PARAXIAL MESODERM

Skull, Vertebral Column, Sternum, Ribs

Intramembranous Ossification frontal, parietal, part of occipital,

maxilla, zygomatic, squamous portion of temporal, palatine, vomer,
mandible.

Endochondrial Ossification petrous & mastoid portion of temporal,

base of occipital, hyoid, styloid process, ear ossicles;
Vertebral column, sternum, ribs.
 VERTEBRAL DEVELOPMENT
&
HOX GENES
* Definite expression
Expression fads out
No expression Vitamin A (Retinoic Acid) is a
signaling molecule. It will causes
a cranial shift if taken early in
development; more thoracic and
less cervical vertebrae. It will
cause a caudal shift if given later
in development; more thoracic
and less lumbar vertebrae.

Klippel-Feil Syndrome/
Brevicollis

Short neck with reduced

number of cervical vertebrae.
 VERTEBRA & RIB DEVELOPMENT
Scleratome Paraxial mesoderm

Neuro-
tube

Rachischisis spinal dysraphism in which the

neurotube and neuroarch fail to fuse dorsally.
 PES EXCAVATUM
(hollow chest)

Over growth of costal cartilages.

Can impair cardiac and respiratory function.
STERNAL DEVELOPMENT & ANOMALIES

Somatic Lateral Plate Mesoderm

Split Sternum

Early Development

Bifid Sternal & Xiphoid

Xiphoid Process Foramen Normal
 PES CARINATUM
(pigeon chest)

An outward bow in the sternum.

Reduces lung function.
Usually seen with Marfans, Osteogenesis imperfecta,
Trisomies 18 and 21.
 APPENDICULAR SKELETON

DERIVED FROM SOMATIC LATERAL PLATE MESODERM

Clavicle, scapula, humerus, radius, ulna, carpal, metacarpal,

phalanges, pelvis, femur, tibia, fibula, tarsal, metatarsal, and phalanges

Intramembranous Ossification Clavicle

Endochondrial (Intracartilaginous) All the other appendicular bones.

 CLEIDOCRANIAL DYSPLASIA

Absence of one or both clavicles

Individuals may have osteopenia (decreased bone density) and may develop
osteoporosis (bones are brittle and prone to fracture).
Women with cleidocranial dysplasia have an increased risk and may require a cesarean
section due to a narrow pelvis preventing passage of the infant's head.
MYOGENESIS MUSCLE DEVELOPMENT
 PARAXIAL MESODERM AND DEVELOPING SOMITES
MYOTOME AND MUSCLE
Recall that paraxial mesoderm differentiates
into the dermatome, myotome, and scleratome.

Somitomeres 44 pairs of which 37 form somites.

First 7 pair do not form somites. They become
striated muscle of the face, jaw and throat
(pharyngeal arches)
Innervated by
Cranial nerves

Somites (paired) give rise to muscles associated with

the axial skeleton.

1-4:occipital part of skull, bones of nose, eye, inner

ear, ocular muscles, tongue muscles.
5-12: cervical region
Innervated by 13-24: thoracic region
Spinal nerves 25-29: lumbar region and leg muscles
30-34: sacral region
35-37: coccygeal region
 SKELETAL MUSCLE
Derived from Paraxial Mesoderm (Myotome)
Transcription factors
Signaling Molecules
Genes

3.
Migration to
MyoD
Somatic Lateral Plate Mesoderm
2. Differentiation

1. Proliferation
FGF, TGF

MRF4
Pax

(Mesoderm)
Wnt 4.
BMP -4 Muscle Fiber
Maturation to
Engrailed (En-1)
Epithelial Cells Muscle Fiber
(Ectoderm)
 Wnt
Dorsalizing Signaling
TRUNK MUSCULATURE

Pax-3

Signaling Molecules
Pax-3 from epithelium

Gene
BMP-4 in mesenchyme cells
Ventral/lateral
Signaling
 Signaling Molecules Gene

PRUNE BELLY X
BMP-4 ventral-lateral signal

Failure of anterior abdominal

musculature to form.
 LIMB MUSCULATURE

Signaling Molecules
Signaling Molecules
from epithelium

Wnt-7 Wnt dorsal muscle signaling

(extensors & abductors)

En Engrailed-1; ventral muscle signaling

(flexors and adductors)

En-1

The dorsal-ventral
diagram is a plane that
is 90 degrees to the
cranial-caudal plane.
QUESTION SET #1
LIMB DEVELOPMENT
 CONGENITAL ANOMALIES OF THE LIMBS
CLINICAL TERMS LIMB DEFECTS

Melia limb Dactyly digit Melia:

Mero part Acrodolichomelia disproportionately large hands or feet

Acro tip Amelia or Ectromelia absence of one or more limbs
Poly extra Hemimelia absence of a pre- or post-axial limb segment
Ectro missing Meromelia part of a limb
A missing Phocomelia short ill formed limb
Brachy or Phoco short Dolichomelia abnormally long limps
Dolicho long Sirenomelia fusion of lower limb buds
Hemi half
Phoco seal like Dactyly:
Syn - fusion
Adactyly absence of digits
Ectrodactyl absence of any number of fingers or toes
Brachydactyly shortened digits
Dolichodactyly abnormally long digits
Polydactyl extra digits or parts of digits
Syndactyly fused digits

Lobster claw (cleft hand or foot) split hand or foot with

central component missing
 CONGENITAL ANOMALIES OF THE LIMBS
WHY?

Etiology of defects General Types of Anomalies

1. Environmental 1. Arrest in development/reduction

A. Hyperthemia 2. Failure of differentiation
B. Retinoic acid 3. Duplication
C. Aspirin 4. Overgrowth/hypertrophy
D. Thalidomide 5. Underdevelopment/hypoplasia
6. Focal defects (amnioti band syndrome)
2. Genetic
 LIMB FORMATION
4th Week

Proximal Anterior Thumb

Distal
Axis

Posterior

Ventral Dorsal Axis

* Limb Buds form by 4th Week. Digits Recognizable by 8th Week

Transcription factors

Dorsolateral
Rotation

Tbx 5

Ventromedial
Rotation
FACTORS INFLUENCING LIMB FORMATION
 APICAL ECTODERMAL RIDGE (AER)

AER - Organizing center for the

Proximal AER proximal-distal
growth of the limb.
Distal
 SIGNALING OF AER GROWTH CENTER

Gene
in mesoderm
Proximal AER
Signaling Molecules
in mesoderm & ectoderm
Distal

Mesoderm Ectoderm Progress Zone just Proximal Distal

beneath AER expresses
FGF-8 FGF-10 & Hox genes.
FGF-10
AER
+ Hox
Shh
FGF-8

ZPA (zone of polarizing activity)

 AMELIA

Signaling Molecules

Mesoderm

Ectoderm
FGF-10 X X
Shh
X FGF-8
X
Defect in Early Limb Bud Development
Fig
Leaf
 ZONE OF POLARIZING ACTIVITY (ZPA)

Cranial

ZPA - Organizing center for the

anterior-posterior (cranial-caudal)
ZPA growth of the limb.
Caudal
 SIGNALING OF ZONE OF POLARIZING ACTIVITY (ZPA)
Anterior/
Cranial

Hox

Posterior/
ZPA
Caudal

Anterior/
Cranial

Mesoderm Progress Zone just

Ectoderm Hox beneath AER expresses
FGF-8
transcription factor.
FGF-10
+ AER
Shh
ZPA FGF-8
Posterior/
Caudal

Gene Signaling Molecules

in mesoderm in mesoderm & ectoderm
 Shh CAUDAL/CRANIAL SIGNALING REGULATION

Anterior/
Cranial

Gli-3
_
Shh gradient

+ Hox

+ Shh

Gli-1
Gene
Posterior/ in mesoderm
Caudal
Signaling Molecules
In mesoderm

Transcription Factors
in mesoderm
 HEMIMELIA
Gli-3 NORMAL SIGNALING
_
+
Shh signal Hox

Gli-1

ABNORMAL SIGNALING

Lower than Gli-3 overexpression

normal

highest Shh

Gli-1

Note the missing radius

ZPA
in the x-ray.
 Gli-3 NORMAL SIGNALING POLYDACTYLY
_
+
Shh signal Hox

Gli-1

Secondary AER site

Anterior/ ABNORMAL SIGNALING

Cranial

lowest Gli-3 underexpression

X
lowest

Mesoderm Gene
highest Shh signal
Signaling Molecules
Gli-1
Transcription Factors
Posterior/
Caudal ZPA
 MEROMELIA
Improper Hox Gene Signaling
NORMAL SIGNALING
Mesoderm

Hox
Hox Ectoderm
FGF-10
Shh
FGF-8 Gene

Signaling Molecules

ABNORMAL SIGNALING
Distal Mesoderm

Hox
Ectoderm
FGF-10 Hox

Cranial Caudal
Shh
FGF-8

Proximal
BMP (bone morphogenic protein)
Another signaling molecule
AER is maintained only at the tips of the digits.

Signaling Molecules
Apoptotic inducing Factors +
FGF from AER

SYNDACTYLY

Fused digits due to insufficient BMPs.

 POLYDACTYLY

Another form of polydactyly due to an abnormal wave of BMP signaling

that induces a duplication of the middle digit.
 LOBSTER CLAW

AER

Central component of hand or foot

missing due to over-expression of BMPs.

Cleft Hand Cleft Foot

ABNORMAL BONE FORMATION SYNDROMES
Marfan Syndrome
Osteogenesis Imperfecta
Achondroplasia
SUMMATION OF LIMB DEVELOPMENT
GERM CELLS INVOLVEMENT
 CELLS FORMING THE LIMBS

Mesoderm/lateral plate

Mesoderm/paraxial
Paraxial mesoderm
Neuroectoderm

Neurocrest

LIMB BUD

Endothelial Cells
&
Smooth Muscle
of blood vessels
Bone
Myoblast migrate into the limb buds and form
dorsal muscle masses consisting of extensors,
abductors and supinators. Innervated by
posterior divisions of nerve plexuses.

Myoblast migrate into the limb buds and form

ventral muscle masses consisting of flexors,
adductors and pronators. Innervated by
anterior divisions of nerve plexuses.

Connective Tissue is responsible for GSE

nerve migration signals. GSA nerves are
the last thing to enter the muscle masses.
QUESTION SET #2