13. Limb Devo Flashcards
areas of somatic mesoderm located on each side of the
embryo.
The Limb Fields
Due to differential expression of_______ genes, the limb fields are localized at distinct axial levels, one for the upper limb and one for the lower limb
Hox
Specific transcription factors are expressed within the upper limb_____ and the lower limb ______
(Tbx5)
Tbx4 & Pitx-1
Limb bud outgrowth is initiated by signaling molecules
_______originating in the _______ mesoderm.
(FGF & Wnt)
intermediate
Limb bud outgrowth is initiated by signaling molecules
(FGF & Wnt) originating in the intermediate mesoderm. These signals induce ______ expression in the appropriate areas of ________ resulting in limb bud formation.
FGF 10
lateral plate mesoderm
forms skeletal elements, fibrous connective tissue and
dermis of the skin (probably vascular endothelium and smooth muscle)
Somatic mesoderm
forms the epidermis of the skin
Surface Ectoderm
migrates into the limb bud forming the skeletal muscle
Somitic (somite derived) mesoderm –
Nerve fibers from ________ of spinal nerves migrate into the limb and become surrounded by neural crest-derived Schwann cells.
ventral primary rami
Limb development occurs along three axes. Limbs elongate and limb segments are formed along the _______ axis.
proximal-distal
Muscles and nerves are organized in
compartments along a _______ axis.
dorsal–ventral
Digits are arranged along an _______ axis.
anterior-posterior
After limb outgrowth is initiated, Fgf 10 produced by the somatic mesoderm of the
bud initiates the secretion of______ (also Fgf4 & 2) in the distal ectoderm. This results in a thickening of the distal ectoderm called the _________
Fgf 8
apical ectodermal ridge(AER).
What defines the location of the ridge at the boundary between the dorsal and ventral surfaces of the limb? T
Differential gene expression in the dorsal and ventral surface ectoderm
acts as a signaling center for the underlying
mesenchyme (originating from somatic mesoderm).
AER
Signals from the AER (primarily Fgf 8) induce the adjacent mesenchyme to proliferate, which creates a
pool of mesenchyme cells that enable the limb ______
to elongate.
_____ signals also inhibit mesenchyme differentiation and is secreated from the mesenchyme adjacent to the AER
to maintain AER function until all limb segments
are formed.
Fgf
Thus a positive Fgf feedback loop occurs between the mesenchyme (Fgf 10) and the AER (Fgf 8).
The arrangement of the digits is achieved by signaling from the_________ on the posterior border of the limb just proximal to the AER.
Zone of Polarizing Activity (ZPA)
The ZPA is an area of somatic mesenchyme on the posterior side of the limb bud that secretes
Sonic hedgehog (Shh)
has been shown to mimic the action of Shh.
Retinoic acid
Expression of Shh from the ZPA initiates the expression of a subset of the Hox genes in the posterior
mesoderm… how does this cause normal digit formation
Expression occurs in an overlapping nested fashion. This expression pattern of Hox genes as well as other signaling molecules
The flat digital plate contains condensations of mesenchyme representing each digit called _____
digital rays
The phalanges and joints will form from digital rays and initially they are joined together by a web of condensed mesenchyme. The AER in the web areas disappears and
triggers apoptosis within the web mesenchyme. This results in digit separation. The AER remains at the
distal tip of the digital ray until all parts of the digit have formed.
How do we get vascular supply to developing muscles in the limbs?
Sprouts from several intersegmental arteries enter the limb bud and form a vascular network within the mesenchyme. Eventually one intersegmental
dominates as the primary axial artery. During development, the vascular network is remodeled into the mature vascular arrangement.
