limb development

Question 1

determining what goes where for limb parts- polarity and specification occurs with 3 things-

Answer 1

TFs (Hox genes)
signaling
gradients (SHH)

Question 2

name the 2 major limb bud organizer regions

Answer 2

AER (apical ectodermal ridge)
ZPA (zone of polarizing activity)

Question 3

AER is thickening of the ___ at the tip of a developing limb bud

Answer 3

ectoderm

Question 4

ZPA is a small group of cells in the ___ of the developing limb bud that provides patterning info through production of a gradient

Answer 4

mesoderm

Question 5

the AER controls patterning along the ___ axis
the ZPA is responsible for ___ patterning of the limb

Answer 5

proximal-distal
anterior-posterior

Question 6

formation of the limb bud was identified using these methods/tools:

Answer 6

1- loss of limb structures upon elimination of certain cells
2- limb generation through transplantation
3- fate mapping with labeling

Question 7

induction of early limb bud (formation of proximal-distal axis)
phase 1 and 2

Answer 7

phase 1: initiation: WNTs and FGFs
- the lateral plate mesodermal cells secrete Fgf10 to initiate limb formation
- restricted expression/stabilization of Fgf10 by Wnts

phase 2: specification- fore and hindlimbs by Tbx4 (hindlimbs) and Tbx5 (forelimbs)

Question 8

the ___ loop (b/w Fgfs and Wnts) initiates the AER and limb bud

Answer 8

feed-forward loop

Question 9

limb type specification by Tbx4 & 5 - Tbxs are involved via a ___

Tbx expression controls the ___ of the limb

Answer 9

gradient

identity (misexpression induces mutations)

Question 10

AER is responsible for the proximal-distal patterning of the limb, this occurs over time through the ___, signals are sent back and forth b/w it and the AER

Answer 10

progress zone

Question 11

2 models for the mesodermal specification of the proximal-distal axis of the limb

Answer 11

1. TIME- cell fate in the limb is determined by the length of time it spends in the progress zone
   
   • the PROGRESSIVE ZONE MODEL- the longer the cells spend in progress zone, the more mitosis underwent to generate more distal structures
2. SPACE- cells are pre-specified
   
   • EARLY ALLOCATION & PROGENITOR EXPANSION MODEL- cell expansion forms the entire early limb bud, which is already specified

unclear which model it really is, could be a combo

Question 12

limb regeneration always follows a ___ to ___ patterning

Answer 12

proximal to distal

Question 13

both proximal and distal surfaces regenerate ___ structures

Answer 13

distal

Question 14

Hox genes help ___ or ___ the proximal-distal patterning (segments) in the limbs as well as the ___ of limb buds along anterior-posterior axis

Answer 14

define or specify
generation

Question 15

Hox genes are involved in limb bud ___ and limb identity ___

Answer 15

formation
determination

Question 16

Anterior-posterior specification of the limb axis:
ZPA, a small block of ___ tissue near posterior junction of the early limb bud is involved in defining the anterior-posterior polarity

Shh is enriched in ___ and able to produce ectopic posterior ___ when transplanted into the early limb bud

Answer 16

mesodermal

ZPA, digits

Question 17

when a ZPA is grafted to an anterior limb bud mesoderm, ___ emerge

Answer 17

mirror duplicated digits

Question 18

generation of dorsal-ventral axis is determined by the ___ components

___ determined the front from the back of the hand (limb) in a simple gradient

Answer 18

ectodermal
Wnt7a

Question 19

name 3 factors involved in coordinating the 3 axxes

Answer 19

1- positive feedback loop between AER and ZPA
2- WNt7a
3- BMPs

Question 20

coordinating the 3 axes:

Wnt7a, which is important for the dorsal limb structure development, can induce ___ expression in combo with ___ to support the posterior digit formation

BMPs shut down and signal from the ___ and inhibit ___ signaling –> growth suppression in all dimension

Answer 20

shh
Fgf4

AER
Wnt7a

Question 21

cell death & the formation of digits and joints

interdigital cell death- genetically programmed sculpting mechanisms

apoptosis induced by various ___

Answer 21

BMP (bone morphogenic proteins)