No abstract

Using immunohistochemical staining, the distribution of connexin40 (Cx40) and connexin43 (Cx43) was studied in rat, guinea pig, porcine, bovine and human hearts. These species display differences in the degree of morphological differentiation of the conduction system. This study was performed in the anticipation that comparison of the distributions of Cx40 and Cx43 in young and adult specimens may provide clues as to the physiological role of connexins in the heart. To a large extent, the distribution patterns of Cx40 and Cx43 are comparable between species. In neonates and adults, Cx43 was immunolocalized throughout the working myocardium, but in the conduction system Cx43 was detected only after birth. Cx40 was found to appear slightly earlier in development than Cx43 and to disappear when levels of Cx43 became more abundant. This time course was seen in working myocardium and in the ventricular conduction system. Together these data suggest that expression of Cx40 induces or facilitates expression of Cx43, while abundant expression of Cx43 in turn leads to suppression of Cx40 expression. The exceptions to this may represent blocks in this potential regulatory sequence. A second conclusion is that Cx40 and Cx43 containing gap junctions appear in the ventricular conduction system from distal to proximal and only after birth. This indicates that terminal differentiation of the conduction system occurs unexpectedly late in development.

Rat (Rattus norvegicus) and spiny mouse (Acomys cahirinus) are closely related murinoid species that mainly differ in the developmental timing of birth. A comparison between the developmental profiles of some characteristic enzymes of the liver of both species was carried out to elucidate the question to what extent are these enzymic profiles and hence the maturation of the liver related to the timing of birth? It was found that these organotypic enzymes first become detectable at the same developmental stage in both species. Likewise, the weaning phase of the enzymic profiles occurs at the same developmental time point in both species. It is argued that both the first appearance and the weaning increase in enzyme activity levels occur at endogenously programmed timepoints with only superimposed effects of hormones. In contrast, the perinatal phase of the enzymic profile is completely dependent on the developmental timing of birth and therefore appears not to be anchored to a particular developmental timepoint, but rather to be dependent on birth-associated (hormonal) adaptation. In accordance with this hypothesis it was found that the morphological development of the liver proceeded independent of the timing of birth. Furthermore, the hormonal regulation of the investigated enzymes was found to be the same in both species. Despite the more advanced state of morphological development of the liver in the spiny mouse at birth, it was found that the inducibility of organotypic gene expression by hormones in spiny mouse fetuses was as limited as in rat fetuses. This observation therefore suggests that the intra-uterine environment is responsible for the limited inducibility of enzymes before birth.

Rat (Rattus norvegicus) and spiny mouse (Acomys cahirinus) are closely related murine species that, due to their altricial (rat) and precocial (spiny mouse) modes of development, differ in the developmental timing of birth. A comparison between the developmental profiles of plasma glucagon, insulin, thyroxine, triiodothyronine, and glucocorticosteroid hormone was carried out to elucidate the question to what extent these hormonal profiles were related to the timing of birth. Although corticosterone is the major circulating glucocorticosteroid in rat, only cortisol was found in the spiny mouse. The onset of increases in glucocorticosteroid and thyroid hormone levels occurred at the same developmental time points in both species. A neonatal increase in triiodothyronine levels was observed in the spiny mouse only. In both species the immediate perinatal period was characterized by decreases in the ratio of insulin and glucagon levels and the level of glucocorticosteroids. The observed developmental patterns of hormonal levels were found to be consistent with the observed developmental pattern of enzymic maturation in the respiratory and gastrointestinal tract, which play a critical role in the adaptation to the extrauterine environment.

Rat and spiny mouse (Acomys cahirinus) are closely related murinoid species that represent altricial (rat) and precocial (spiny mouse) modes of development. The late intrauterine developmental stages of the spiny mouse therefore seem comparable to the early extra-uterine developmental stages of the rat. To elucidate the question to what extent the development of the lung is related to the developmental timing of birth, we have studied some enzymes involved in the de novo synthesis of phosphatidylcholine. Of the enzymes studied, cholinephosphate cytidylyltransferase shows peaks in activity in the perinatal period (rat and spiny mouse) and at the beginning of the 3rd postnatal week (rat only). This enzyme fulfils the requirements for a developmental parameter best as changes in activity of this enzyme can be correlated with phases of cell proliferation and surface expansion in the lung of the rat. The single peak of cholinephosphate cytidylyltransferase activity in the spiny mouse as well as microscopical examination of the lung support the hypothesis that the processes of proliferation and surface expansion, which occur consecutively in the rat, develop concurrently in the spiny mouse.

In adult rat liver, glutamate dehydrogenase is present in high concentrations around the terminal portal (zone 1) and hepatic (zone 3) veins, whereas its concentration is low in the intermediate zone. Although the size and staining intensity of the periportal glutamate dehydrogenase-positive compartment are less than those of the pericentral compartment, it can expand under appropriate endocrine conditions, leading to a homogeneous distribution. At birth, glutamate dehydrogenase is also homogeneously distributed. Glutamate dehydrogenase disappears from the periportal compartment during the first postnatal week and reappears in that compartment after weaning. These observations indicate an independent regulation of glutamate dehydrogenase levels in the periportal and pericentral zone. The size of the periportal glutamate dehydrogenase-containing zone is appreciably smaller than that of carbamoylphosphate synthetase, whereas the pericentral glutamate dehydrogenase-containing zone is appreciably larger than that of glutamine synthetase. The heterogeneous distribution of glutamate dehydrogenase suggests the possibility that, under normal conditions, deamination of glutamate prevails in the periportal compartment and amination of glutamate in the pericentral compartment.

The distribution pattern of creatine kinase (EC 2.7.3.2) isozymes in developing chicken heart was studied by immunohistochemistry. Creatine kinase M, which is absent from adult heart, is transiently expressed between 4 and 11 days of incubation. During that period, numerous muscular cells in the roof and septum of the atrium, in the interventricular septum and on top of the trabeculae cordis and at the rim of the outflow tract stain strongly with a polyclonal antibody that is specific for the M subunit. In the ventricle and outflow tract, the M-positive cells are found mainly subendocardially and in the right half, at the transition of conducting and working myocytes. Creatine kinase B, which is the predominant adult isozyme, is initially expressed to a high concentration in a small group of disperse myocardial cells in upstream part of the inflow tract. When compared to the expression pattern of cardiac myosin heavy chains, the observed creatine kinase expression pattern suggests that M-positive cells are mainly found in areas that participate in the formation of cardiac conductive tissue, whereas B-positive cells are first found in areas that are involved in the generation of cardiac rhythm.

Rat (Raitus norvegicus)and spiny mouse (Acomys cahirinus)are closely related species that mainly differ in the developmental timing of birth. A comparison between the developmental profiles of some characteristic enzymes of the small intestine (lactase and sucrase) and of the pancreas (amylase) of both species was carried out to elucidate the question to what extent these enzymic profiles and hence the maturation of these organs was related to the process of birth. It was found that these organ-specific enzymes become first detectable at the same developmental stage in both species. Likewise, the weaning phase of the enzymic profiles occurred at the same developmental time point in both species. It is argued that both the first appearance and the weaning increase in enzyme activity follow an inherent biological program that can only be modulated by hormones. In contrast, the perinatal phase of the enzymic profile is completely dependent on the developmental timing of birth, and therefore appears not to be anchored to a particular developmental time point but rather to be dependent on birth-associated (hormonal) adaptation. In accordance with this hypothesis it was found that the development of the microscopic anatomy of the small intestine proceeded independently of the functional adaptation of the intestine to the process of birth.