Hyaluronan-Mediated Aggregation of Limb Bud Mesenchyme and Mesenchymal Condensation during Chondrogenesis

ABSTRACT Matemal diabetes is associated in humans and rats with an increased risk for fetal growth abnormalities and malformations. Therefore, the effect of maternal diabetes on expression of genes that regulate fetal growth and differentiation is of considerable interest. Developmental growth is regulated in part by the expression and availability of insulin-like growth factors (IGFs). Postnatal expression of a subset of the IGFs and IGF binding proteins (IGFBPs) has been demonstrated to be regulated in response to diabetes and other metabolic conditions. We used in situ hybridization to analyze the effect of maternal diabetes, induced by streptozotocin (STZ) prior to mating, upon prenatal rat IGF and IGFBP mRNA expression. At gestational day (GD) 14, the most striking effect of maternal diabetes on fetal IGF/IGFBP gene expression was a marked increase in the abundance of IGFBP-1 mRNA within the liver primordia of fetuses isolated from diabetic dams compared to age-matched controls. This upregulation cannot be entirely due to the approximately one-half-day delay in fetal development (based on limb bud staging) associated with maternal diabetes, as there was no gross difference in the level of IGFBP-1 mRNA between GD13 and GD14 control fetal livers. In contrast, the fetal mRNA expression patterns of IGF-I, IGF-II and IGFBP-2, -3, -4, -5 and -6 were not grossly altered by maternal diabetes. These data are consistent with the hypothesis that IGFBP-1 produced within the fetal liver and secreted into fetal circulation may play a role in regulating rat fetal growth.

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W. T. Astbury and Ross G. Harrison: the search for the molecular determination of form in the developing embryo

Notes and Records the Royal Society journal of the history of science ◽

10.1098/rsnr.1980.0017 ◽

1980 ◽

Vol 35 (2) ◽

pp. 195-219 ◽

Cited By ~ 3

Keyword(s):

Royal Society ◽

Limb Bud ◽

Amphibian Embryo ◽

X Ray ◽

Biological Phenomena ◽

Biology I ◽

Series Of Experiments ◽

Molecular Patterns ◽

Molecular Determination

Amongst the Fellows elected to the Royal Society in 1941 were W. T. Astbury for his studies using X-ray analysis to study the structures of natural fibres, and amongst the Foreign Members elected that year was Ross G. Harrison for his contributions to embryology. Astbury and Harrison were very different in temperament, and worked in very different fields on either side of the Atlantic, yet they were united in their approach to the study of biological phenomena. Both Astbury and Harrison believed that the organization and form of biological materials whether wool fibres or the limb-bud in an amphibian embryo depended on molecular structure and pattern. Moreover both were concerned with dynamic aspects of form; Astbury’s greatest achievement was to demonstrate the dynamic, reversible folding and stretching of proteins in the k-m-e-f group, and Harrison looked to changing molecular patterns to account for changing symmetries in the developing embryo. It was this common approach that brought them together and led to Harrison spending a brief month in Leeds where they and K. M. Rudall performed what have been described as ‘truly progressive experiments in molecular biology’. I believe this short series of experiments illuminates the character and work of both Harrison and Astbury and illustrates the difficulties, practical and conceptual, in carrying out ‘progressive experiments’. I shall begin by reviewing briefly the embryological background of the time before going on to discuss in detail the approaches of Harrison and Astbury to their work and the outcome of their collaboration.

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