limb development Flashcards
determining what goes where for limb parts- polarity and specification occurs with 3 things-
TFs (Hox genes)
signaling
gradients (SHH)
name the 2 major limb bud organizer regions
AER (apical ectodermal ridge)
ZPA (zone of polarizing activity)
AER is thickening of the ___ at the tip of a developing limb bud
ectoderm
ZPA is a small group of cells in the ___ of the developing limb bud that provides patterning info through production of a gradient
mesoderm
the AER controls patterning along the ___ axis
the ZPA is responsible for ___ patterning of the limb
proximal-distal
anterior-posterior
formation of the limb bud was identified using these methods/tools:
1- loss of limb structures upon elimination of certain cells
2- limb generation through transplantation
3- fate mapping with labeling
induction of early limb bud (formation of proximal-distal axis)
phase 1 and 2
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)
the ___ loop (b/w Fgfs and Wnts) initiates the AER and limb bud
feed-forward loop
limb type specification by Tbx4 & 5 - Tbxs are involved via a ___
Tbx expression controls the ___ of the limb
gradient
identity (misexpression induces mutations)
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
progress zone
2 models for the mesodermal specification of the proximal-distal axis of the limb
- 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
- 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
limb regeneration always follows a ___ to ___ patterning
proximal to distal
both proximal and distal surfaces regenerate ___ structures
distal
Hox genes help ___ or ___ the proximal-distal patterning (segments) in the limbs as well as the ___ of limb buds along anterior-posterior axis
define or specify
generation
Hox genes are involved in limb bud ___ and limb identity ___
formation
determination
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
mesodermal
ZPA, digits
when a ZPA is grafted to an anterior limb bud mesoderm, ___ emerge
mirror duplicated digits
generation of dorsal-ventral axis is determined by the ___ components
___ determined the front from the back of the hand (limb) in a simple gradient
ectodermal
Wnt7a
name 3 factors involved in coordinating the 3 axxes
1- positive feedback loop between AER and ZPA
2- WNt7a
3- BMPs
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
shh
Fgf4
AER
Wnt7a
cell death & the formation of digits and joints
interdigital cell death- genetically programmed sculpting mechanisms
apoptosis induced by various ___
BMP (bone morphogenic proteins)
