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.

An Anatomical study of Cleft hand in North – East population of Assam

Introduction: Cleft hand or Ectrodactyly or Split Hand is a rare form of congenital hand disorder in which there is deficiancy of one or more central rays of the hand. The hand presents with a V-shaped gap situated in the centre of the palm. The condition may occur alone or maybe associated with anomalies of foot, syndactly, polydactyly, triphalangeal thumb, transverse bones in the hand or maybe part of Ectrodactyly Ectodermal dysplasia Cleft (ECC) Syndrome. Aims and Objectives: To find out the sex ratio and incidence of laterality (unilateral or bilateral) of cleft hand in North East population of Assam. Subjects and Methods: This study included 31 children between age group of 3 years to 8 years with hand deformities who were brought to the Plastic Surgery Department, Gauhati Medical College, Guwahati for aesthetic correction within a time span of 2 years. Only those cases who had central defects of hand were included & those with other syndromic anomalies were excluded. For this detailed clinical and radiological examination was done to evaluate the extent of bone or tissue involvement and to find out any syndromic association of the condition. Results: Out of 31 cases, 10 cases were had Unilateral and 21 cases had Bilateral Cleft Hands. It was seen that out of 31 cases, 22 were males and only 09 were females indicating that male to female ratio of the deformity is 2.44 .Thus, males were more affected than females. Conclusion: Most of the cases presented with absence of the middle finger and central tissue of the affected hand since birth. The embryological basis has been highlighted to throw light into such a catastrophe where both males and females were affected and showed unilateral or bilateral involvement of the hand leading to cosmetic and functional debility. Therefore, the study revealed that males were more affected than females and bilateral involvement of the hands were common than unilateral involvement

Morphogenesis of the Hindlimb Digits and 5-FU induced Apoptotic Changes / 체질인류학회지

During the morphogenesis of the hindlimb and the digits of the rat, apoptosis has a crucial role to make their normal shape. In this study, apoptotic changes of the hindlimb from GD 13.5 to GD 17.5 were observed and compared with 5 -FU treated group to reveal the mechanism of teratogenic action of 5 -FU. The results were as follows; 1. The mean body weight of rat fetuses was decreased significantly in the 5 -FU treated group. 2. Congenital anomalies of the hindlimb digits were cleft foot, syndactyly and short digits, and the occurance rate of congenital anomalies was 58.1%, in which right -sided anomalies was 49.1% and left -sided anomalies was 18.9%. 3. Normal morphogenesis of the hindlimb digits was as follows; initially, hindlimb bud appeared at the lateral wall of lumbar somite on GD 10.5, grown as an elliptical mass proximodistally on GD 13.5, flattening and digital rays formation on GD 14.5, interdigital notches appeared on GD 15.5, interdigital spaces formation and interphalageal joints formation on GD 16.5, and deepening of interdigital spaces and elongation of digits on GD 17.5. 4. 5 -FU inhibited differentiation and growth of hindlimb bud initially, but its effect on development of hindlimb was disappeared after GD 15.5. According to the above results, it is considered that 5 -FU has an inhibitory effect on differentiation and growth of hindlimb of rat fetuses, and the TUNEL immunohistochemical method is much available to detect normal morphogenesis of an organ and to detect the mechanism of action of various teratogens.