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M. Maden
Abbreviations
RA
Retinoic acid
RAR
Retinoic acid receptor
RARE
Retinoic acid response element
RALDH Retinaldehyde dehydrogenase
ZPA
Zone of polarizing activity
AP
Anteroposterior
DV
Dorsoventral
PD
Proximodistal
DEAB
Diethylaminobenzaldehyde
GFP
Green fluorescent protein
AER
Apical ectodermal ridge
EGFR
Epidermal growth factor receptor
nAG
Newt anterior gradient protein
HPLC
High pressure liquid chromatography
Introduction
How the embryo becomes so precisely patterned or how a regenerating organism
knows how to precisely replace lost appendages is an intriguing question. How do
cells know what to differentiate into at the right time and at the right place? How
do a group of apparently homogeneous cells in the limb bud, arranged in the shape
of a cone, grow out in a distal direction and sequentially form the upper limb bones
(humerus or femur), then the lower limb bones (radius and ulna or tibia and fibula),
and then the wrist and digits? How do cells at the amputation plane, which make the
blastema, know what is missing so they can replace exactly what was removed?
Morphogens, or signaling molecules that act in the form of a gradient during
development and regeneration were proposed long ago by embryologists and regeneration biologists as an underlying answer to these questions. For example, Morgan
(1901) proposed the existence of a gradient of ‘formative substances’ to explain perfect regeneration. Boveri (1901) and Hörstadius (1935) proposed that the sea urchin
embryo was patterned by opposing animal and vegetal gradients. Child (1941) proposed that metabolic gradients were the basis of development (cited in Ephrussi and
Johnston 2004). The concept was put into concrete terms by Lewis Wolpert in his
seminal paper on positional information (Wolpert 1969). Wolpert proposed that cells
could measure their position within a field by reference to a gradient of a morphogen
which diffuses across the field from a source. Cells measure the concentration of that
morphogen and this gives ‘positional information’ to the cells and induces a different
differentiation state, such that a high concentration might induce the differentiation
of a humerus, a medium concentration might induce the differentiation of a radius
and ulna, and a low concentration might induce the differentiation of digits.
M. Maden
Abbreviations
RA
Retinoic acid
RAR
Retinoic acid receptor
RARE
Retinoic acid response element
RALDH Retinaldehyde dehydrogenase
ZPA
Zone of polarizing activity
AP
Anteroposterior
DV
Dorsoventral
PD
Proximodistal
DEAB
Diethylaminobenzaldehyde
GFP
Green fluorescent protein
AER
Apical ectodermal ridge
EGFR
Epidermal growth factor receptor
nAG
Newt anterior gradient protein
HPLC
High pressure liquid chromatography
Introduction
How the embryo becomes so precisely patterned or how a regenerating organism
knows how to precisely replace lost appendages is an intriguing question. How do
cells know what to differentiate into at the right time and at the right place? How
do a group of apparently homogeneous cells in the limb bud, arranged in the shape
of a cone, grow out in a distal direction and sequentially form the upper limb bones
(humerus or femur), then the lower limb bones (radius and ulna or tibia and fibula),
and then the wrist and digits? How do cells at the amputation plane, which make the
blastema, know what is missing so they can replace exactly what was removed?
Morphogens, or signaling molecules that act in the form of a gradient during
development and regeneration were proposed long ago by embryologists and regeneration biologists as an underlying answer to these questions. For example, Morgan
(1901) proposed the existence of a gradient of ‘formative substances’ to explain perfect regeneration. Boveri (1901) and Hörstadius (1935) proposed that the sea urchin
embryo was patterned by opposing animal and vegetal gradients. Child (1941) proposed that metabolic gradients were the basis of development (cited in Ephrussi and
Johnston 2004). The concept was put into concrete terms by Lewis Wolpert in his
seminal paper on positional information (Wolpert 1969). Wolpert proposed that cells
could measure their position within a field by reference to a gradient of a morphogen
which diffuses across the field from a source. Cells measure the concentration of that
morphogen and this gives ‘positional information’ to the cells and induces a different
differentiation state, such that a high concentration might induce the differentiation
of a humerus, a medium concentration might induce the differentiation of a radius
and ulna, and a low concentration might induce the differentiation of digits.