Charles Philippe Leblond : biography
It is of interest that autoradiographic studies by Leblond during this period also settled a controversy regarding the cellular site of synthesis of ribonucleic acid. Using radiolabeled cytidine in some forty cell types, he and his colleagues were the first to demonstrate decisively that RNA is continuously synthesized in the nucleus and then migrates to the cytoplasm.M. Amano and C.P. Leblond. Comparison of the specific activity time curves of ribonucleic acid in chromatin, nucleolus and cytoplasm. Exp. Cell Res. 1960, 20, 250 253.M. Amano, C.P. Leblond and N.J. Nadler. Radioautographic analysis of nuclear RNA in mouse cells revealing three pools with different turnover times. Exp. Cell Res. 1965, 38, 314 340.
Role of the Golgi Apparatus in Protein Glycosylation
A majority of body proteins is glycosylated, although the proportion of carbohydrates in proteins is quite variable. Leblond had shown in earlier studies that the Golgi region in most cell types was dramatically stained by the periodic acid-Schiff staining technique, which is specially directed to carbohydrate-rich proteins carrying 1,2 glycols.C.P. Leblond. Distribution of periodic acid reactive carbohydrates in the adult rat. Am. J. Anat. 1950, 86, 1. In the electron microscope, using the periodic acid silver technique, there was a gradient of staining intensity from the cis to the trans side of the Golgi apparatus, suggesting that carbohydrate residues were added to proteins at this site.A. Rambourg, W. Hernandez and C.P. Leblond. Detection of periodic acidreactive carbohydrate in Colgi saccules. J. Cell Biol. 1969, 40, 395 414.
To test this hypothesis, light and then EM autoradiographic studies were carried out by Leblond and Neutra in 1966 after injecting rats with 3H-glucose or 3H-galactose.M. Neutra and C.P. Leblond. Synthesis of the carbohydrate of mucus in the Golgi complex, as shown by electron microscope radioautography of goblet cells from rats injected with 3H-glucose. J. Cell Biol. 1966, 30, 119 136.M. Neutra and C.P. Leblond. Radioautographic comparison of the uptake of 3H-galactose and 3H glucose in the Golgi region of various cells secreting glycoproteins or mucopolysaccarides. J. Cell Biol. 1966, 30, 137 150. Within ten minutes, the label was dramatically localized to the Golgi apparatus of intestinal goblet cells, indicating that this was the cellular site of addition of sugar residues in the synthesis of the carbohydrate side chains of mucous glycoproteins.
This discovery had a tremendous impact on the scientific community, being the first evidence for a functional role of the Golgi apparatus in the synthetic process.
Other classics include: identification of how skeletal bones grow through osteoblast deposition and osteoclast remodeling,Leblond CP, Wilkinson GW, Belanger LF, Robichon J. Radio-autographic visualization of bone formation in the rat. Am J Anat. 1950 Mar;86(2):289-341. early discovery of the biogenesis and metabolism of thyroxineGross J, Leblond CP. Metabolism of the thyroid hormone in the rat as shown by physiological doses of labeled thyroxine. J Biol Chem. 1950 Jun;184(2):489-500. and detection of triiodothyronine,Gross J, Leblond CP. The presence of free iodinated compounds in the thyroid and their passage into the circulation. Endocrinology. 1951 Jun;48(6):714-25. early prediction of DNA semiconservative replicationStevens CE, Daoust R, Leblond CP. Rate of synthesis of deoxyribonucleic acid and mitotic rate in liver and intestine. J Biol Chem. 1953 May;202(1):177-86. published days after the Watson and Crick Nature article,J. D. Watson and F. H. C. Crick. A Structure for Deoxyribose Nucleic Acid. April 25, 1953, Nature, 171, 737-738 the discovery of axonal transport,Droz B, Leblond CP. Migration of proteins along the axons of the sciatic nerve. Science. 1962 Sep 28;137:1047-8. the Warshawsky et al.Warshawsky H, Leblond CP, Droz B. Synthesis and migration of proteins in the cells of the exocrine pancreas as revealed by specific activity determination from radioautographs. J Cell Biol. 1963 Jan;16:1-24. finding that nascent proteins are processed from the rough endoplasmic reticulum through the Golgi apparatus into pancreatic zymogen granules (made in hot competition with the Palade lab at Rockefeller University), the first realization that the Golgi apparatus is the site of terminal glycosylation,Peterson M, Leblond CP. Synthesis of Complex Carboydrates in the Golgi region, as shown by radioautography after injection of labeled glucose. J Cell Biol. 1964 Apr;21:143-8. the discovery of the cell coat,Rambourg A, Neutra M, Leblond CP. Presence of a "cell coat" rich in carbohydrate at the surface of cells in the rat. Anat Rec. 1966 Jan;154(1):41-71. the cellular biogenesis of collagen,Weinstock M, Leblond CP.Synthesis, migration, and release of precursor collagen by odontoblasts as visualized by radioautography after (3H)proline administration. J Cell Biol. 1974 Jan;60(1):92-127. and new insights into the ultrastructure of basement membrane.Inoue S, Leblond CP, Laurie GW. Ultrastructure of Reichert’s membrane, a multilayered basement membrane in the parietal wall of the rat yolk sac. J Cell Biol. 1983 Nov;97(5 Pt 1):1524-37.