The Limb Bud
First appear as pairs of bilateral buds.
Forelimbs appear earlier then hindlimbs.
Arise adjacent to defined regions (limb fields) of lateral plate mesoderm.
Core of mesenchyme
Covered by ectoderm
Truncation of limb structures by AER removal can be rescued by FGF8.
AER/FGF8 maintains adjacent mesenchymal cells (Progress Zone) in mitosis
(proliferative state) and prevents cell death (apoptosis)
Series of interact
Series of interactions between the AER and underlying mesenchyme (Progress
Mesoderm/Progress Zone cells produce FGF10, which induces and maintains the
AER/FGF8 maintains adjacent mesenchymal cells (Progress Zone) in mito
Fore & Hind Limbs Tbx5 vs Tbx4
What do Tbx5 and Tbx4 do?
KO Tbx5 no forelimbs; But
Ectopic Tbx4 expression rescues forelimbs
Pitx1 expression Hindlimb specifier?
Tbx5 and Tbx4 drive limb outgrowth
Tbx4 + Pitx1 together may regulate hindlimb identity
Limb Bud Formation
Somatic LPM proliferation
Somitic cell migration and proliferation
Cells accumulate beneath ectoderm
Why does this occur only in the limb regions?
What defines a limb field?
Dual gradient (FGF/Wnt vs. RA) defines determination front
Notch and Wnt oscillations in the PSM (fast)
Stabilized signals/slow oscillations in the determined somites
Mesp2 Mediator of Notch Signalling
Somite patterning signals
Multiple signals regulate formation of the dermatome, myotome and sclerotome.
Wnt1, Wnt3a factors from ectoderm and neural tube specify myogenic transcription
in dorsal (epaxial) myotome.
Neural tube factors (NT3, Wnt1) and Wn
Somite development & derivatives
Cells within a somite have different fates.
Somitic cells form different intermediate (and transient) structures:
Dermomyotome (Pax3) dermis and muscles
Sclerotome (Pax1) vertebrae and ribs
Evolutionary Conserved System
High degree of similarity in structures and mechanisms
Intensively studied model system!
Develop in proximo-distal
Three Major Limb Axes
Fore & Hind Limbs - What is the
Fore and hind limb bud mesenchyme express different transcription factor genes
(Forelimb -Tbx5 and Hindlimb - Tbx4).
Signals are the same (FGFs) but cell responses differ.
FGFs induce limbs
FGF in forelimb fi