test 2 limbs

Question 1

Outgrowth of the embryonic body wall, consisting of mesenchyme derived from the somites and the lateral plate mesoderm. These precursors accumulate and proliferate under the epidermis to create a bulge called the ____

Answer 1

limb bud

Question 2

limb buds are formed from ___ and ___

Answer 2

lateral plate mesoderm- somatic mesoderm and the ectoderm

paraxial mesoderm- somites - myotome (muscle of limbs)

Question 3

___ are muscle precursors and are the only limb component derived from somites rather than somatic lateral plate mesoderm

Answer 3

Migrating hypaxial cells

Question 4

Migrating hypaxial cells are muscle precursors and are the only limb component derived from ___ rather than ___

Answer 4

somites

somatic lateral plate mesoderm

Question 5

The mesenchyme of the limb bud is derived from the mesoderm:

Answer 5

somites -hypaxial cells (muscle precursors)

somatic lateral plate mesoderm (skeletal precursors)

Question 6

what determines where limbs are formed

Answer 6

Hox genes that provide positional information in the developing embryo are good candidates.

Question 7

mammalian hox genes are ___ to fly hox genes

Answer 7

4 orthologous paralogs in mammals

Question 8

where does forelimb form

Answer 8

where HoxC6 stops

Question 9

Where does hind limb form

Answer 9

where HoxC8 stops

Question 10

what three genes determine limb location

Answer 10

HoxB5, HoxC6, HoxC8

Question 11

explain why no forelimb in python

Answer 11

HoxC6 starts at top therefore no place where it stops= no forelimbs

HoxC8 goes from top almost all the way down= hindlimbs very far down, residual nubs

these genes are expressed throughout the trunk starting from the hindlimb up to the first cervical vertebrae. A sharp boundary of HOXC8 is detected near the future hindlimb. Expansion of HOXC6 and HOXC8 expression in python embryos can account for extended thorax and loss of fore limbs.

Question 12

Expansion of ___ and ___ expression in python embryos can account for extended thorax and loss of forelimbs.

Answer 12

HOXC6 HOXC8

Question 13

A gradient of ___ along the anterior-posterior axis may activate specific combination of Hox genes to specify the limb fields

Answer 13

retinoic acid

Question 14

Retinoic acids role in limb development

Answer 14

critical for the initiation of limb bud outgrowth.

gradient of retinoic acid along the anterior-posterior axis might activate specific combination of Hox genes in particular cells and specify them to become part of the limb field.

Question 15

Limb identity may depend on the axial level at which it emerges.

___ is sufficient to trigger limb bud formation.

Answer 15

FGF10

fibroblast growth factor

Question 16

Local application of FGFs to the anterior flank induces development of a wing, and FGF applied to posterior flank induces a leg. This suggested that limb identity of the additional limb may depend ___

Answer 16

on the axial level at which it emerge.

Question 17

Ectopic limbs located in the mid-flank appear ___, possessing characteristics of both wings and legs.

Answer 17

chimeric

Question 18

Hox genes are transcription factors that contain a ___ where Tbox genes are transcription factors that contain a ___

Answer 18

homeobox DNA binding domain

Tbox DNA binding domain

Question 19

Tbx5 makes ___ where Tbx4 makes ___

Answer 19

forelimb

hindlimb

Question 20

What gene leads to hind limb?

Answer 20

Tbx4

the expression of Tbox is controlled by FGF 10

Tbox5 inhibits Tbox 4 and works with Hox Code to determine which Tbox is expressed

Question 21

What gene leads to front limb

Answer 21

Tbx5

the expression of Tbox is controlled by FGF 10

Tbox5 inhibits Tbox 4 and works with Hox Code to determine which Tbox is expressed

Question 22

Ectopic limbs located in the mid-flank appear chimeric for ___ expression.

Answer 22

Tbx5 and Tbx4

Question 23

the signal for limb bud formation comes from the lateral plate mesoderm cells secreting ___

Answer 23

FGF10.

which triggers the expression of Tbox 5 or Tbox 4

Question 24

The early limb bud has two major components -

Answer 24

a core of loose mesenchymal mesoderm cells

an epithelial ectodermal layer

Question 25

The limb mesenchyme signals (via \_\_\_) the overlying ectodermal to elongate and thicken, to form the \_\_\_**.**

Answer 25

**FGF10** **apical ectodermal ridge (AER)**

Question 26

AER

Answer 26

**apical ectodermal ridge (AER)** ## Footnote **The ridge of the AER runs along the distal margin of the limb bud.** **The factor secreted by the mesenchyme to induce the AER is FGF10.** Outgrowth and differentiation of the limb depend upon inductive interactions between the AER and the underlying limb mesenchyme.

Question 27

Outgrowth and differentiation of the limb depend upon inductive interactions between the ___ and the underlying limb mesenchyme.

Answer 27

AER **apical ectodermal ridge**

Question 28

**The factor secreted by the mesenchyme to induce the AER is \_\_\_**

Answer 28

**FGF10**.

Question 29

Examples of reciprocal signaling between Mesoderm and AER (Ectoderm)

Answer 29

If the **AER is removed**, the mesoderm **stops dividing**. If a **supernumerary AER** is grafted adjacent to a developing limb, a **supernumerary limb results.** If forelimb mesoderm is **replaced by hindlimb** mesoderm the AER will direct development of the grafted limb into a **hindlimb.** If limb bud **mesoderm is removed** from an early limb bud and replaced by non-limb mesoderm, the **AER regresses** and the mesoderm ceases proliferation.

Question 30

Molecules of the FGF family appear to be responsible for the AER activity. If AER is removed and replaced by a bead soaked in FGF a normal limb development will form. ___ is expressed at the right place and the right time to play this role.

Answer 30

FGF8

Question 31

what are two models to explain limb patterning?

Answer 31

termporally pre patterned

Question 32

limb is broken into three zones:

Answer 32

stylopod zeugopod autopod

Question 33

The zone immediately adjacent to the AER is the \_\_\_

Answer 33

**progress zone (PZ)**.

Question 34

The AER is believed to maintain ___ cells in an undifferentiated state, stimulating their division

Answer 34

progress zone (PZ)

Question 35

AER produces ___ which stimulates the ___ to \_\_\_

Answer 35

FGF8 progress zone to produce differentiated cells, the cells that leave first and differentiate first become the humerus (stylopod) then zeugopod, then autopod

Question 36

The ___ participate in the establishment of the proximal-distal axis of the limb

Answer 36

progress zone

Question 37

During outgrowth of the limb, cells of the ___ are assigned progressively more distal positional identities.

Answer 37

progress zone

Question 38

Cells leaving the progress zone differentiate and their positional value will depend on the time at which they leave the progress zone. explain

Answer 38

cells that leave PZ first are the cells that will turn into the humerus, closest to the body. will form cartilage and bone before the cells that leave the PZ last that become fingers

Question 39

The first cells leaving the progress zone form ___ structures, the cells that have undergone numerous divisions in the progress zone become the more \_\_\_.

Answer 39

proximal (humerus) distal structures (fingers)

Question 40

If AER is removed then \_\_\_

Answer 40

limbs will stop developing, if removed early on humerus will form is AER removed later humerus and radius will form ect.

Question 41

what makes flipper babies

Answer 41

thalidomide phocomelia Thalidomide blocks cell growth in the progress zone despite continued exposure to AER-derived FGF8

Question 42

phocomelia

Answer 42

flipper babies from exposure to thalidomide ## Footnote Thalidomide blocks cell growth in the progress zone despite continued exposure to AER-derived FGF8 cells in the progress zone never end up outside the range of FGF8. Instead, the entire PZ is progressively assuming distal characteristics. -hand only instead of arms and hands

Question 43

\_\_\_ is essential for joints formation and for the separation of the digits.

Answer 43

apoptosis (programmed cell death)

Question 44

The signal for apoptosis is provided by ___ expressed in the interdigital mesenchyme.

Answer 44

Bone Morphogenetic Proteins (BMPs)

Question 45

In the duck, cell death is inhibited by a \_\_\_, expressed between the digits.

Answer 45

BMP inhibitor, Gremlin, keeps webbing

Question 46

Abnormal persistence of soft tissues between the digits or lack of separation of the digits is a condition known as \_\_\_

Answer 46

**_syndactyly_**.

Question 47

**_syndactyly_**

Answer 47

Abnormal persistence of soft tissues between the digits or lack of separation of the digits is a condition known as

Question 48

three axes of limb

Answer 48

proximal-distal, anterior-posterior and dorsal-ventral

Question 49

The AER extends from the anterior to posterior along the dorsal/ventral boundary of the growing limb. Immediately under the AER is the \_\_\_.

Answer 49

progress zone

Question 50

Located in the posterior mesoderm is the\_\_\_ that controls the ___ polarity of the limb.

Answer 50

ZPA zone of polarizing activity anterior-posterior

Question 51

The __ axis is specified by a timing mechanism and the dorsal-ventral axis is specified by the ectoderm. The AER, PZ and ZPA cooperate, so that limb patterning and growth are partly dependent of their coordinated function.

Answer 51

proximal-distal

Question 52

The ___ axis is specified by the posterior mesoderm of the limb bud known as the ***zone of polarizing activity (ZPA******)***.

Answer 52

anterior-posterior

Question 53

The pattern of digit formation is dependent upon the \_\_\_.

Answer 53

zone of polarizing activity ZPA

Question 54

Anterior transplantation of ZPA induces ___ of the digits.

Answer 54

duplication

Question 55

\_\_\_, a secreted protein, mediates the polarizing activity of the ZPA.

Answer 55

***Sonic hedgehog (Shh)***

Question 56

*Why doesn't FGF8 activate Shh expression in the entire mesenchyme beneath the AER?*

Answer 56

only cells in the zone of polarizing activity produce **Gremlin.** This **inhibits BMP.** This makes the cells **differential competence** which allows then to innertact with Shh and activate a FGF4-Shh feedback loop.

Question 57

In the limb bud the ___ polarity is determined by the **ectoderm by \_\_\_**

Answer 57

dorsal-ventral palm vs back of hand Wnt7a

Question 58

The\_\_\_ gene is restricted to the **dorsal** ectoderm of the limb bud.

Answer 58

**Wnt7a**

Question 59

is Wnt 7a is removed from limb bud what will happen

Answer 59

no dorsal region would have palms on both side of hand

Question 60

how does Sox 9 lead to bone

Answer 60

mesenchyme + sox 9 = cartilage which is then replaced by bone during endochondral ossification