Dealy C N, Scranton V, Cheng H C
Department of Anatomy, University of Connecticut Health Center, Farmington, Connecticut, 06030, USA.
Dev Biol. 1998 Oct 1;202(1):43-55. doi: 10.1006/dbio.1998.8988.
We have examined the distribution of transforming growth factor-alpha (TGF-alpha), epidermal growth factor (EGF), and the chicken EGF receptor (c-erbB), in embryonic chick limbs. Prior to limb budding, TGF-alpha is present in prospective limb-forming mesoderm and in prospective apical ectodermal ridge (AER)-forming ectoderm, but is not detected in non-limb-forming flank mesoderm or ectoderm, nor in presumptive non-AER-forming limb ectoderm, suggesting possible roles in initial limb formation and AER induction. Consistent with this possibility, TGF-alpha is present in the mesoderm of the wing buds of the amelic chick mutants limbless and wingless, which form and bud normally, but is absent from limbless and wingless ectoderm, which fails to form an AER. TGF-alpha and EGF are present in the AER of the developing limb, and TGF-alpha, EGF, and c-erbB are present in the underlying subridge mesoderm, suggesting possible roles in reciprocal AER/subridge mesoderm interactions required for limb outgrowth. We found that exogenous TGF-alpha and EGF can promote the outgrowth of limb mesoderm in the absence of the AER in vitro and can also promote the outgrowth of limbless and wingless wing bud explants. EGF is present in ventral but not dorsal limb ectoderm, suggesting a role for EGF in specification of ventral ectoderm. TGF-alpha and EGF are not detected in the differentiating cartilaginous elements or muscle primordia of the limb, suggesting that cessation of TGF-alpha and EGF expression may be required for cartilage and muscle formation. We have found that exogenous TGF-alpha and EGF inhibit chondrogenesis and myogenesis of limb mesenchyme in vitro. Together these results indicate that signaling through the EGF receptor via endogenous TGF-alpha and EGF may be important for initial limb formation, AER induction, outgrowth of limb mesoderm, and regulation of limb chondrogenic and myogenic differentiation.
我们研究了转化生长因子-α（TGF-α）、表皮生长因子（EGF）和鸡表皮生长因子受体（c-erbB）在鸡胚肢体中的分布。在肢体芽形成之前，TGF-α存在于预期形成肢体的中胚层和预期形成顶端外胚层嵴（AER）的外胚层中，但在未形成肢体的侧翼中胚层或外胚层中未检测到，在假定不形成AER的肢体外胚层中也未检测到，这表明其在肢体初始形成和AER诱导中可能发挥作用。与此可能性一致的是，TGF-α存在于无肢和无翅鸡突变体的翼芽中胚层中，这些突变体的肢体正常形成和出芽，但在未能形成AER的无肢和无翅外胚层中不存在。TGF-α和EGF存在于发育中肢体的AER中，TGF-α、EGF和c-erbB存在于其下方的嵴下中胚层中，这表明它们在肢体生长所需的AER/嵴下中胚层相互作用中可能发挥作用。我们发现，外源性TGF-α和EGF在体外可促进无AER情况下肢体中胚层的生长，也可促进无肢和无翅翼芽外植体的生长。EGF存在于肢体腹侧而非背侧外胚层中，这表明EGF在腹侧外胚层的特化中发挥作用。在肢体分化的软骨成分或肌肉原基中未检测到TGF-α和EGF，这表明软骨和肌肉形成可能需要停止TGF-α和EGF的表达。我们发现，外源性TGF-α和EGF在体外可抑制肢体间充质的软骨生成和肌生成。这些结果共同表明，内源性TGF-α和EGF通过表皮生长因子受体发出的信号可能对肢体的初始形成、AER诱导、肢体中胚层的生长以及肢体软骨生成和肌生成分化的调节很重要。
