Various classifications of congenital anomalies of the extremities and spine have been proposed and are in use. Some are based on anatomy, some on embryology, presumed etiology, or therapeutical approach. An ideal classification would help better understanding and treatment of various kinds of congenital anomalies. It should be simple, logical, and broad enough to include most of the congenital anomalies with minimal confusion. In this paper, we are proposing a functional classification of congenital anomalies of the extremities and spine based upon the concept that development of each organ is processed by differentiation and modulation according to the genetically determined information and by control mechanism at particular moment. We classified congenital anomalies into structural failure where quality of certain tissue is abnormal and functional failure where control mechanisms failed to regulate organogenesis. We divided structural failure into generalized and localized form while we divided functional failure into differentiation and modulation failures. Differentiation failure was subdivided as either forrnation failure or segmentation failure. Formation failure, segmentation failure, and modulation failure were specified according to the timing of failed inhibition and topography.
Classification ; Embryology ; Extremities ; Logic ; Organogenesis ; Spine

OBJECTIVEThis study was designed to explore the effects of zinc on bone development.

METHODSForelimbs of mice with 16 d gestation were cultured by a rotating device.

RESULTSContents of OC and (45)Ca and activities of AKP in the bone tissues cultured at zinc-deficiency media and at media with 120 micro mol/L of Zn(2+) decreased significantly. Synthesis of OC, absorption of calcium and activities of AKP in the bone tissues cultures at media with 45 and 70 micro mol/L of Zn(2+) increased significantly. Radiograph of bone tissues showed that length of long bone cultured at zinc-deficiency media and at media with 120 micro mol/L of Zn(2+) shortened and their density reduced, and those cultured at media with 45 and 70 micro mol/L of zinc increased, as compared with self-control bone. Histological analysis showed the death of bone cells and loss of stroma in the bone tissues cultured at media with 120 micro mol/L of Zn(2+), and active proliferation and differentiation of bone cells, and secretion and synthesis of osteoid increased in the bone tissues cultured at media with 45 and 70 micro mol/L of zinc.

CONCLUSIONSAdequate supplementation of zinc could promote formation and development of bone tissues and deficiency or excess of zinc could alter their growth and development and normal metabolism.

Animals ; Bone Density ; drug effects ; Bone Development ; drug effects ; Calcium ; metabolism ; Embryo, Mammalian ; drug effects ; physiology ; Extremities ; embryology ; Female ; Insulin-Like Growth Factor II ; Male ; Mice ; Proteins ; metabolism ; Zinc ; pharmacology

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.
Animals ; Apoptosis ; Body Patterning ; Bone Morphogenetic Proteins/biosynthesis* ; Developmental Biology ; Ectoderm/metabolism* ; Extremities/embryology* ; Fibroblast Growth Factor 10/metabolism* ; Fibroblast Growth Factors/biosynthesis* ; Gene Expression Regulation ; Hedgehog Proteins/biosynthesis* ; Homeodomain Proteins/biosynthesis* ; Mesoderm/metabolism* ; Mice ; Signal Transduction ; Wnt Proteins/biosynthesis*