"Embryogenesis is in some way a model system. It has always been distinguished by the exactitude even punctitio, of its anatomical descriptions. An experiment by one of the great masters of embryology could be made the text of a discourse on scientific method. But something is wrong, or has been wrong. There is no theory of development in the sense in which Mendelism is a theory that accounts for the results of breeding experiments. There has therefore been little sense of progression or timeliness about embryological research. Of many papers delivered at embryological meetings, however good they may be in themselves . . . one too often feels that they might have been delivered five years beforehand without making anyone much the wiser, or deferred for five years without making anyone conscious of a great loss" (1). This feeling of frustration so incisively conveyed by these considerations by P. Medawar, pervaded, in the forties, the field of experimental embryology which had been enthusiastically acclaimed in the mid-thirties, when the upper lip of the amphibian blastopore brought this area of research to the forefront of the biological stage. The side branch of experimental neuroembryology, which had stemmed out from the common tree and was entirely devoted to the study of the tropic interrelations between neuronal cell populations and between these and the innervated organs and tissues, was then in its initial vigorous growth phase. It in turn suffered from a sharp decrease in the enthusiasm that had inflamed the pioneers in this field, ever since R. G. Harrison delivered his celebrated lecture on this topic at the Royal Society in London in 1935 (2). Although the alternate "wax and wane" cycles are the rule rather than the exception in all fields of human endeavor, in that of biological sciences the "wane" is all too often indicative of a justified loss of faith in the rational and methodical approach that had at first raised so much hope. A brief account of the state-of-the-art of experimental neuroembryology in the

https://science.sciencemag.org/content/sci/237/4819/1154.full.pdf

The nerve growth factor 35 years later

Inheritance of a mutation at the Rb-1 locus, which has been mapped to band q14 of human chromosome 13, results in predisposition to retinoblastoma. Cloned DNA segments homologous to arbitrary loci of human chromosome 13 and which reveal polymorphic restriction endonuclease recognition sequences, have been used to look for somatic genetic events that might occur during tumorigenesis. A comparison of constitutional and tumour genotypes from several cases indicates that tumorigenesis may result from the development of homozygosity for the mutant allele at the Rb-1 locus. The homozygosity in these cases results from mitotic nondisjunction, resulting in loss of the homologous wild-type chromosome, or from a mitotic recombination event.

Expression of recessive alleles by chromosomal mechanisms in retinoblastoma

High-resolution banding techniques for the study of human chromosomes have revealed that the malignant cells of most tumors analyzed have characteristic chromosomal defects. Translocations of the same chromosome segments with precise breakpoints occur in many leukemias and lymphomas, and a specific chromosome band is deleted in several carcinomas. Trisomy, or the occurrence of a particular chromosome in triplicate, is the only abnormality observed in a few neoplasias. It is proposed that chromosomal rearrangements play a central role in human neoplasia and may exert their effects through related genomic mechanisms. Thus, a translocation could serve to place an oncogene next to an activating DNA sequence, a deletion to eliminate an oncogene repressor, and trisomy to carry extra gene dosage.

http://science.sciencemag.org/content/sci/221/4607/227.full.pdf

The Chromosomal Basis of Human Neoplasia

https://www.cell.com/cell/pdf/0092-8674(87)90158-9.pdf

A genetic linkage map of the human genome

"Embryogenesis is in some way a model system. It has always been distinguished by the exactitude even puctilio, of its anatomical descriptions. An experiment by one of the great masters of embryology could be made the text of a discourse on scientific method. But something is wrong, or has been wrong. There is no theory of development in the sense in which Mendelism is a theory that accounts for the results of breeding experiments. There has therefore been little sense of progression or timeliness about embryological research. Of many papers delivered at embryological meetings, however good they may be in themselves.. .one too often feels that they might have been delivered five years beforehand without making anyone much the wiser, or deferred for five years without making anyone conscious of a great loss". (1) This feeling of frustration so incisively conveyed by these considerations by P. Medawar, prevaded, in the forties, the field of experimental embryology which had been enthusiastically acclaimed in the mid-thirties, when the upper lip of the amphibian blastopore brought this area of research to the forefront of the biological stage. The side branch of experimental neuroembryology, which had stemmed out from the common tree and was entirely devoted to the study of the trophic interrelations between neuronal cell populations and between these and the innervated organs and tissues was then in its initial vigorous growth phase. It in turn suffered from a sharp decrease in the enthusiasm that had inflamed the pioneers in this field, ever since R. G. Harrison delivered his celebrated lecture on this topic at the Royal Society in London in 1935 (2). Although the alternate 'wax and wane' cycles are the rule rather than the exception in all fields of human endeavor, in that of biological sciences the 'wane' is all too often indicative of a justified loss of faith in the rational and methodical approach that had at first raised so much hope. A brief account of the state-of-the-art of experimental neuroembryology in the forties, when interest in this approach to the study of the developing nervous system was waning, is a prerequisite for understanding the sudden unforseeable turn of events which resulted in the discovery of the Nerve Growth Factor. EXPERIMENTAL NEUROEMBRYOLOGY IN THE EARLY FORTIES

/pdf/the-nerve-growth-factor-thirty-five-years-later-1xj6rh45ve.pdf

The nerve growth factor: thirty-five years later.

Use of a 4.5-kilobase-pair (kb) segment of single-copy DNA from a human genomic library as a hybridization probe of genomic human DNAs revealed allelic Taq I restriction fragments 10.6, 11.8, and 14.6 kb long. Among 12 unrelated individuals, all 6 males exhibited the 14.6-kb fragment in addition to one of the other fragments. Three of the females displayed 10.6- and 11.8-kb fragments, and the other three displayed only one fragment length; none had the 14.6-kb fragment. Hybridization of this probe to Taq I-digested DNAs from human-rodent hybrid cell lines (which have partial complements of human chromosomes) demonstrated segregation of the 14.6-kb fragment with the human Y chromosome and segregation of the 10.6- and 11.8-kb fragments with the human X chromosome. Furthermore, hybridization of this probe to Taq I-digested DNAs from 48 members of a single kindred revealed Y-linked inheritance of the 14.6-kb fragment and X-linked inheritance of the 10.6- and 11.8-kb fragments. These experiments demonstrate homology between single-copy sequences on the human X and Y chromosomes.

http://www.pnas.org/content/79/17/5352.full.pdf

Single-copy sequence hybridizes to polymorphic and homologous loci on human X and Y chromosomes.

The gene for the mitochondrial enzyme ornithine transcarbamylase was mapped to the short arm of the X chromosome by in situ hybridization experiments, with DNA complementary to the human ornithine transcarbamylase gene used as a probe. A series of cell lines with X chromosome abnormalities was used to localize the gene to band Xp21.1. Because the gene maps near the Duchenne muscular dystrophy locus, the ornithine transcarbamylase probe may be useful in carrier detection and prenatal diagnosis of Duchenne muscular dystrophy as well as of ornithine transcarbamylase deficiency.

https://science.sciencemag.org/content/sci/226/4675/698.full.pdf

Human ornithine transcarbamylase locus mapped to band Xp21.1 near the Duchenne muscular dystrophy locus

Fragments of the recently cloned human gene for the beta subunit of nerve growth factor (beta-NGF) were used as hybridization probes in analyzing two sets of rodent-human somatic cell hybrids for the presence of human beta-NGF sequences. Results from the first set of hybrids assigned the human beta-NGF gene to chromosome 1 and ruled out the presence of sequences of comparable homology on any other chromosome. With the second set of hybrids, which contained seven different, but overlapping, regions of chromosome 1, the NGF locus was mapped to band 1p22.

The human gene for the β subunit of nerve growth factor is located on the proximal short arm of chromosome 1

The human cellular homolog of the transforming DNA sequence isolated from the bladder carcinoma cell line EJ was localized on the short arm of human chromosome 11 by Southern blot analysis of human-rodent hybrid cell DNA. This locus contains human sequences homologous to the Harvey murine sarcoma virus v-Ha-ras oncogene.

http://science.sciencemag.org/content/sci/219/4584/498.full.pdf

Oncogene from human EJ bladder carcinoma is located on the short arm of chromosome 11

A locus responsible for a restriction fragment length polymorphism (RFLP) has been identified by hybridization of Eco RI fragments to the random human DNA sequence in recombinant plasmid pAW101. We have examined DNA extracted from 20 human X Chinese hamster somatic cell hybrids for the presence of sequences homologous to the human insert in pAW101. The hybrids were derived from six different human donors, five of whom were heterozygous, producing two bands on Southern transfers. The presence of homologous sequences in the hybrids correlated exclusively with the presence of human chromosome 14. Three hybrids contained chromosome 14 in a frequency of greater than one per cell and were positive for two alleles. Two hybrids contained only the distal half of the long arm of 14 as part of a translocation and were still positive. These results assign the first highly polymorphic random RFPL locus (D14S1) to region q21 leads to qter of chromosome 14.

B de Martinville

Papers

Single-copy sequence hybridizes to polymorphic and homologous loci on human X and Y chromosomes.

Human ornithine transcarbamylase locus mapped to band Xp21.1 near the Duchenne muscular dystrophy locus

The human gene for the β subunit of nerve growth factor is located on the proximal short arm of chromosome 1

Oncogene from human EJ bladder carcinoma is located on the short arm of chromosome 11

Assignment of first random restriction fragment length polymorphism (RFLP) locus ((D14S1) to a region of human chromosome 14.