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pattern formation Flashcards

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1
Q

Stylopod

A

Humerus

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2
Q

Zeugopod

A

Ulna and radius

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3
Q

Autopod

A

Metacarpals and Digits

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4
Q

Steps in tetrapod limp development

A

a. specification
b. determination
c. induction (EMT)
d. initiation
e. outgrowth
f. patterning

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5
Q

somites (sclerotome)

A

cartilage -> bone

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6
Q

somites (myotome)

A

skeletal muscle

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7
Q

somites (dermatome)

A

dermis, connective tissues

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8
Q

neural crest cells

A

neurons

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9
Q

surface ectoderm

A

skin epidermis and specializations

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10
Q

embryonic origin of tetrapod limb

A

somites (sclerotome, myotome, dermatome), neural crest cells, surface ectoderm

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11
Q

genes responsible for specification of forelimb development

A

HOX5, HOX7, HOX9

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12
Q

genes responsible for specification of primitive lateral plate mesoderm

A

PRX1, FOXF1

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13
Q

genes responsible for determination of forelimb development

A

BMP2, BMP7

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14
Q

This defines the specification of the limb bud and forelimb field within the lateral plate mesoderm (LPM)

A

HOX6

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15
Q

Events in Limb Field Specification

A

a. Lateral plate mesoderm (LPM) regionalizes into forelimb and hindlimb fields.

b. Expression of Hox genes defines limb-forming regions.

c. Tbx5 (forelimb) and Tbx4 (hindlimb) are expressed.

d. Retinoic acid (RA) helps define limb identity.

e. Limb field is still flat (called limb disk).

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16
Q

The lateral plate mesoderm (LPM) becomes regionally specified into:

A
  • Anterior LPM (ALPM)
  • Posterior LPM (PLPM)
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17
Q

What happens in determination?

A

a. Limb field cells become irreversibly committed to forming a limb.

b. Continued expression of Tbx5/Tbx4 solidifies fate.

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18
Q

The flattened area within the limb field, before the limb visibly protrudes.

A

Limb disk

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19
Q

What happens in induction?

A

Epithelial-mesenchymal transition in mesoderm for limb bud cells.

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20
Q

It sets the foundation for limb bud formation by identifying the exact layer of mesoderm that will give rise to limb structures

A

Specification of the somatic mesoderm

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21
Q

posterior lateral plate mesoderm (PLPM) splits into two layers:

A
  1. Splanchnic mesoderm (adjacent to the endoderm)
  2. Somatic mesoderm (adjacent to the ectoderm)
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22
Q

gene expression in specification of the somatic mesoderm

A

FoxF1 off, Irx3 on → somatic mesoderm.

FoxF1 maintained → splanchnic mesoderm.

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23
Q

Expressed in the primitive lateral plate mesoderm

A

Fox1

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24
Q

Activates FGF8 in the ectoderm to form the Apical Ectodermal Ridge (AER).

A

Fgf10

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25
Activate FGF10
Tbx5 (for forelimbs) and Tbx4 (for hindlimbs)
26
Activates Tbx5/4 and FGF10 in the mesoderm
Wnt2b (wing field) / Wnt8c (leg filed)
27
Regulates the proximal-distal axis and HOX gene expression.
Retinoic acid (RA)
28
TF that drives expression of leg-specific genes
PITX1
29
Limb arises as a condensation of cells from
the lateral plate mesoderm and its ectodermal covering
30
Mesenchyme cells from the limb field will
move from the lateral plate mesoderm and somites towards the outer ectodermal layer.
31
The limb fields have been defined by
differential Hox expression and RA
32
What growth factor is secreted by mesenchyme cells to initiate limb bud formation?
FGF10, which activates the overlying ectoderm.
33
What does the activated ectoderm secrete in response to FGF10?
FGF8, which maintains mesenchymal proliferation.
34
What is the role of FGF8 in limb development?
Keeps mesenchyme cells proliferating and induces Shh expression in the posterior region.
35
What gene marks the anterior-posterior boundary in limb buds and is expressed below somite 19?
Hoxb8
36
What is the role of Shh in the limb bud?
It induces FGF4 expression in the posterior region, contributing to the feedback loop that maintains FGF8 expression.
37
What is the function of FGF4 in limb development?
Reinforces FGF8 expression in the ectoderm (posterior AER), maintaining limb outgrowth.
38
Where is Wnt7a expressed, and what is its role?
Expressed only in the dorsal ectoderm; helps maintain Lmx1b expression for dorsal limb identity.
39
Expressed only in the ventral ectoderm; define the dorsal-ventral axis (back of hand vs. palm).
En1
40
What organizer region controls the Proximal-Distal (PD) axis in limb development?
Apical Ectodermal Ridge (AER)
41
What organizer region controls the Anterior-Posterior (AP) axis in limb development?
Zone of Polarizing Activity (ZPA)
42
What happens when the Zone of Polarizing Activity (ZPA) is transplanted to the anterior side of a limb bud?
It induces the formation of a mirror-image limb, showing ZPA’s role in specifying the anterior-posterior (AP) axis.
43
How does the timing of AER removal affect limb development?
- If the AER is removed early, only proximal limb components (e.g., humerus) form. - The longer the AER remains, the more distal components (e.g., radius, digits) develop.
44
role of AER in PD Axis establishment
Maintains mesenchymal proliferation in the underlying Progress Zone (PZ)
45
when AER is removed
limb development ceases
46
Extra AER
Wing is duplicated
47
Nonlimb mesoderm
AER regresses; limb development ceases
48
AER replaced by FGF bead
Normal wing (FGF4 or FGF8 can replace AER)
49
Limb polarity in anterior-posterior axis
HOX, ZPA (Shh), Tbx
50
Limb polarity in proximal-distal axis
FGFS and HOX
51
Limb polarity in dorsal-ventral axis
Wnt7a and Lmx1
52
Establish patterning along the anterior/posterior axis and proximal-distal axis
Hox genes
53
Limb polarity of AP axis Help cells to interpret their anterior/posterior coordinates.
ZPA (via Sonic hedgehog or Shh)
54
Shh creates a gradient from posterior to anterior
This gradient patterns the anterior-posterior axis of the limb: - High Shh → posterior digits (digit 4 or 5) - Low Shh → anterior digits (digit 1, thumb)
55
Limb polarity of AP axis Determine anterior vs. posterior limb development.
Tbx5 and Tbx4
56
Limb polarity of PD axis Mediate interactions between the AER and PZ involved in limb growth and differentiation.
Fibroblast growth factor (Fgf)
57
expressed earlier, more anterior embryonic locations
3' Hox genes
58
expressed later and more posteriorly
5' Hox genes
59
exhibit spatial and temporal colinearity
Hox cluster genes (A-D)
60
forelimb Hox genes
A and D
61
hindlimb Hox genes
C and D
62
Hox9 (near 3')
Scapula
63
Hox10
Humerus
64
Hox11
Ulna and radius
65
Hox12
Metacarpals
66
Hox13 (near 5')
Digits/Fingers
67
Differential Hox gene expression Phase I Stylopod
Hoxa9, Hoxa10
68
Differential Hox gene expression Phase II Zeugopod
Hoxd-9, d-10, d-11, d-12, d-13
69
Differential Hox gene expression Phase III Autopod
Hoxa-13 and Hoxd-13
70
resulting from homozygous HOXD-13 null mutation
Human with synpolydactyly
71
expressed only in the anterior portion of the embryo, arising from the lateral plate mesoderm
Tbx5
72
expressed only in the posterior regions of the lateral plate mesoderm, causing development of a hindlimb.
Tbx4
73
If an FGF bead placed in the posterior region where Tbx4 is being expressed
formation of another hindlimb
74
mimicking the activity of the mesenchyme cells
FGF bead
75
What does PCD stand for in limb development?
Programmed Cell Death (apoptosis), which helps shape the limb by removing unnecessary cells.
76
Where does PCD occur in the developing chick limb?
In posterior necrotic zone (PNZ) for others in the anterior necrotic zone (ANZ), and interdigital zones (IDZs).
77
What is the function of BMP4 in limb development?
BMP4 induces apoptosis in the interdigital mesenchyme to separate the digits.
78
What is the role of Gremlin in limb development?
Gremlin is a BMP inhibitor; it blocks BMP4 activity to prevent apoptosis, allowing webbing (as in duck feet). Thus minimal cell death
79
What happens if BMP4-induced apoptosis fails between digits?
Webbed digits form—a condition called syndactyly
80
Chick differentiation of the limb
BMP4 → Activates SMADs → Triggers interdigital apoptosis
81
Duck differentiation of the limb
BMP4 present, but Gremlin blocks BMP signaling Prevents cell death → webbing remains
82
In the chicken foot primordia is involved in determining the identities of digits 1 to 4 at late developmental stages
Graded BMP signaling from the interdigital (ID) mesenchyme
83
intracellular mediator of BMP signal transduction
SMAD
84
From which cells do skeletal elements of the limb arise?
From mesenchymal cells of the limb bud.
85
What is the first step in skeletal differentiation in the limb?
Mesenchymal condensation in the central region of the proximal limb bud.
86
What do mesenchymal cells become during limb development?
They differentiate into cartilage cells, forming the cartilage model for future bones.
87
What is the order of appearance of limb skeletal elements?
scapula, humerus, ulna and digits V and IV, then radius and digits III, II, and I.
88
When does ossification begin in limb development?
After the cartilaginous form is well established.
89
Where do all muscle precursors in the limb come from?
From the myotomes of the somites.
90
What are the stages of muscle differentiation in the limb?
1. Formation of extensor and flexor muscle masses 2. Formation of individual muscle primordia 3. Reconstruction of the primordia from phylogenetically primitive to species-specific 4. Development of definitive form; muscle joining with tendons
91
When does muscle formation begin in relation to skeletal development?
Just after the skeletal elements begin to form.
92
Functional limb composed of multiple differentiated components:
**Stylopod** - Humerus in forelimb - Femur in hindlimb **Zeugopod** - Radius & Ulna in forelimb - Tibia & Fibula in hindlimb **Autopod** - Metacarpals and Digits in forelimb - Metatarsals and Digits in hindlimb

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