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Alterations in phosphofructokinase isoenzymes during early human development. Establishment of adult organ-specific patterns.

ABSTRACT: Human 6-phosphofructokinase (EC 2.7.1.11) exists in tetrameric isoenzymic forms composed of muscle (M), liver (L) and platelet (P) subunits, which are under separate genetic control. In the adult, the proportion of these subunits in different organs reflects the relative activity of glycolysis versus gluconeogenesis. To elucidate the developmental basis for the observed distribution, we investigated the isoenzymic transitions of phosphofructokinase in human foetuses (12-40 weeks' gestation) by using high-resolution chromatography and monoclonal antibodies. We studied skeletal muscle, heart, liver and brain because these organs show very different glycolytic fluxes and isoenzymic patterns in adult individuals. Our results demonstrate that there is no unique 'foetal' form of phosphofructokinase in humans, but all three loci are variably expressed in all foetal organs during early gestation. As development proceeds, muscle and liver isoenzyme patterns show dramatic changes, with disappearance of P and L subunits in muscle and transient reappearance of M and P subunits in liver; in contrast, phosphofructokinase isoenzymes change little in brain and heart. Most changes occur at mid-gestation and near term, and adult isoenzyme patterns are expressed at birth, indicating that organ differentiation is complete. These studies show that phosphofructokinase undergoes changes of isoenzyme patterns similar to, but not identical with, those of other multilocus isoenzyme systems of glycolysis. The observed changes probably reflect changing patterns of gene expression, with repression of some loci and activation of others.

SUBMITTER: Davidson M

PROVIDER: S-EPMC1152306 | biostudies-other | 1983 Sep

REPOSITORIES: biostudies-other

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Project description:The development of precise neural circuits in the brain requires spontaneous patterns of neural activity prior to functional maturation. In the rodent cerebral cortex patchwork and wave patterns of activity develop in somatosensory and visual regions, respectively, and are present at birth. However, whether such activity patterns occur in non-eutherian mammals, as well as when and how they arise during development remain open questions relevant to understand brain formation in health and disease. Since the onset of patterned cortical activity is challenging to study prenatally in eutherians, here we offer a new approach in a minimally invasive manner using marsupial dunnarts, whose cortex forms postnatally. We discovered similar patchwork and travelling waves in the dunnart somatosensory and visual cortices at stage 27 (equivalent to newborn mice), and examined progressively earlier stages of development to determine their onset and how they first emerge. We observed that these patterns of activity emerge in a region-specific and sequential manner, becoming evident as early as stage 24 in somatosensory and stage 25 in visual cortices (equivalent to embryonic day 16 and 17, respectively, in mice), as cortical layers establish and thalamic axons innervate the cortex. In addition to sculpting synaptic connections of existing circuits, evolutionarily conserved patterns of neural activity could therefore help regulate early events in cortical development.Significance statementRegion-specific patterns of neural activity are present at birth in rodents and are thought to refine synaptic connections during critical periods of cerebral cortex development. Marsupials are born much more immature than rodents, allowing the investigation of how these patterns arise in vivo. We discovered that cortical activity patterns are remarkably similar in marsupial dunnarts and rodents, and that they emerge very early, before cortical neurogenesis is complete. Moreover, they arise from the outset in different patterns specific to somatosensory and visual areas (i.e., patchworks and waves) indicating they may also play evolutionarily conserved roles in cortical regionalization during development.

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Alterations in phosphofructokinase isoenzymes during early human development. Establishment of adult organ-specific patterns.

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