Apical ectodermal ridge regulates three principal axes of the developing limb / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Understanding limb development not only gives insights into the outgrowth and differentiation of the limb, but also has clinical relevance. Limb development begins with two paired limb buds (forelimb and hindlimb buds), which are initially undifferentiated mesenchymal cells tipped with a thickening of the ectoderm, termed the apical ectodermal ridge (AER). As a transitional embryonic structure, the AER undergoes four stages and contributes to multiple axes of limb development through the coordination of signalling centres, feedback loops, and other cell activities by secretory signalling and the activation of gene expression. Within the scope of proximodistal patterning, it is understood that while fibroblast growth factors (FGFs) function sequentially over time as primary components of the AER signalling process, there is still no consensus on models that would explain proximodistal patterning itself. In anteroposterior patterning, the AER has a dual-direction regulation by which it promotes the sonic hedgehog (Shh) gene expression in the zone of polarizing activity (ZPA) for proliferation, and inhibits Shh expression in the anterior mesenchyme. In dorsoventral patterning, the AER activates Engrailed-1 (En1) expression, and thus represses Wnt family member 7a (Wnt7a) expression in the ventral ectoderm by the expression of Fgfs, Sp6/8, and bone morphogenetic protein (Bmp) genes. The AER also plays a vital role in shaping the individual digits, since levels of Fgf4/8 and Bmps expressed in the AER affect digit patterning by controlling apoptosis. In summary, the knowledge of crosstalk within AER among the three main axes is essential to understand limb growth and pattern formation, as the development of its areas proceeds simultaneously.

Apical ectodermal ridge regulates three principal axes of the developing limb / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Understanding limb development not only gives insights into the outgrowth and differentiation of the limb, but also has clinical relevance. Limb development begins with two paired limb buds (forelimb and hindlimb buds), which are initially undifferentiated mesenchymal cells tipped with a thickening of the ectoderm, termed the apical ectodermal ridge (AER). As a transitional embryonic structure, the AER undergoes four stages and contributes to multiple axes of limb development through the coordination of signalling centres, feedback loops, and other cell activities by secretory signalling and the activation of gene expression. Within the scope of proximodistal patterning, it is understood that while fibroblast growth factors (FGFs) function sequentially over time as primary components of the AER signalling process, there is still no consensus on models that would explain proximodistal patterning itself. In anteroposterior patterning, the AER has a dual-direction regulation by which it promotes the sonic hedgehog (Shh) gene expression in the zone of polarizing activity (ZPA) for proliferation, and inhibits Shh expression in the anterior mesenchyme. In dorsoventral patterning, the AER activates Engrailed-1 (En1) expression, and thus represses Wnt family member 7a (Wnt7a) expression in the ventral ectoderm by the expression of Fgfs, Sp6/8, and bone morphogenetic protein (Bmp) genes. The AER also plays a vital role in shaping the individual digits, since levels of Fgf4/8 and Bmps expressed in the AER affect digit patterning by controlling apoptosis. In summary, the knowledge of crosstalk within AER among the three main axes is essential to understand limb growth and pattern formation, as the development of its areas proceeds simultaneously.

Polydactyly and genes.

Pediatricians deal with cases with the congenital malformations and malformation syndromes interest many of them. A lot of information about genes involved in development is available now. Genetics of hand development and genes involved in polydactyly syndromes is discussed in this article as a prototype to know about genetics of malformations: how it is studied and what is known. Genetic and chromosomal defects are often associated with congenital malformations. Polydactyly is one of the commonly seen malformations and genetic defects of many malformation syndromes associated with polydactyly are known. The role of genetic defect in polydactyly syndromes and the correlation between genotypes and phenotypes is discussed in this review article.

Changes of Apoptosis After X-irradiation During the Hindlimb Development in the Rat Fetus / 체질인류학회지

Ionizing radiation exerts harmful effect during the limb development, but the exact mechanism is still largely unknown. In this study, 2 Gy of X-ray irradiated to the rat fetuses on gestation day of 13.7 when the hindlimb buds appear, and sacrificed at GD 14.7, GD 15.7 and GD 16.7, respectively. To reveal the changes of apoptotic figures between control and experimental groups, TUNEL immunohistochemistry and confocal laser scanning microscopy were carried. Mean body weight of fetuses of irradiated groups were decreased significantly compared to the control group. Numerical digit anomalies and asymmetries between right and left sides were increased significantly in the irradiated group compared to control group. Some digit anomalies were increased significantly in the right side. Radiation-induced decrement of the density of apoptotic figures on GD 14.7 was presumed to be related with foot and digit anomalies.

EFFECT OF DIFFERENT CONCENTRATION OF TRICHOSTATIN A ON CHICKEN WING BUD DEVELOPMENT / 解剖学报

Objective To investigate the reaction of the limbs treated with different concentration of Trichostatin A(75?mol/L,750 ?mol/L,1.5mmol/L),a histone deacetylase(HDAC)-inhibitor.This may be useful to improve our understanding of the role of chromatin remodelling and epigenetic control of gene expression patterns and ultimately the development of drugs against cancer. Methods Using the chicken embryonic limb as an experimental model.The embryos received grafts of TSA soaked beads or PBS control beads into the right forelimb buds.Then they were submitted to in situ hybridization with probes and apoptosis test.Results TSA could modulate the expression of some myogenesis related genes,MyoD and Myf5 during chicken myogenesis.Using apoptosis staining methods,there was no significant apoptosis in the TSA(75?mol/L) treated embryos.However the induction of morphological changes and apoptosis at specific stage was possible with high concentration of TSA.Conclusion TSA(75?mol/L) regulates certain important transcriptional targets and strongly control muscle differentiation.Increasing the concentration of TSA(≥750?mol/L) can induce apoptosis and embryonic limb malformations.Chicken limb development can serve as a convenient in vivo model for studying the effect of HDAC inhibitors.

Retinoic acid in development and regeneration.

Retinoids are low molecular weight, lipophilic derivatives of vitamin A which have profound effects upon the development of various embryonic systems. Here I review the effects on developing and regenerating limbs, regenerating amphibian tails and the developing central nervous system (CNS). In the regenerating amphibian limb, retinoids can proximalize, posteriorize and ventralize the axes of the blastema. In the chick limb bud retinoids can only posteriorize the tissue. In the regenerating amphibian tail retinoids can homeotically transformtail tissue into hindlimb tissue. In the developing and regenerating limb retinoic acid has been detected endogenously, confirming that this molecule plays a role in the generation of pattern and we have shown that limbs cannot develop in the absence of retinoic acid. In the developing CNS retinoic acid specifically affects the hindbrain where it causes a transformation of anterior rhombomeres into more posterior ones. Again, endogenous retinoic acid has been detected in the CNS and in the absence of retinoids the posterior hindbrain has been found to be affected. The effects of retinoids on the CNS are most likely to be mediated via the Hox genes acting in the mesoderm after gastrulation. It has also been proposed that the establishment of the head-to-tail axis in the mesoderm is established by retinoic acid. These data show that retinoids play an important role in both the development and regeneration of various systems in the embryo and post-embryonically.