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PubMed2005

Trade-offs in detecting evolutionarily constrained sequence by comparative genomics.

As whole-genome sequencing efforts extend beyond more traditional model organisms to include a deep diversity of species, comparative genomic analyses will be further empowered to reveal insights into the human genome and its evolution. The discovery and annotation of functional genomic elements is a necessary step toward a detailed understanding of our biology, and sequence comparisons have proven to be an integral tool for that task. This review is structured to broadly reflect the statistical challenges in discriminating these functional elements from the bulk of the genome that has evolved neutrally. Specifically, we review the comparative genomics literature in terms of specificity, sensitivity, and phylogenetic scope, as well as the trade-offs that relate these factors in standard analyses. We consider the impact of an expanding diversity of orthologous sequences on our ability to resolve functional elements. This impact is assessed through both recent comparative analyses of deep alignments and mathematical modeling.

Animals↗
PubMed1994

Holophaga foetida gen. nov., sp. nov., a new, homoacetogenic bacterium degrading methoxylated aromatic compounds.

A polyphasic approach was used in which genotypic and phenotypic properties of a gram-negative, obligately anaerobic, rod-shaped bacterium isolated from a black anoxic freshwater mud sample were determined. Based on these results, the name Holophaga foetida gen. nov., sp. nov. is proposed. This microorganism produced dimethylsulfide and methanethiol during growth on trimethoxybenzoate or syringate. The only other compounds utilized were pyruvate and trihydroxybenzenes such as gallate, phloroglucinol, or pyrogallol. The aromatic compounds were degraded to acetate. Although comparison of the signature nucleotide pattern of the five established subclasses of Proteobacteria with the 16S rDNA sequence of Holophaga foetida revealed a relationship to members of the delta-subclass, the phylogenetic position within the radiation of this class is so deep and dependent upon the number and selection of reference sequences that its affiliation to the Proteobacteria must be considered tentative. The type strain is H. foetida strain TMBS4 (DSM 6591).

Acetates↗
PubMed2006

Abnormal melt curve profile during prothrombin 20210G --> A analysis due to the 20209C --> T variant.

The common factor II 20210G --> A mutation, located in the 3'-untranslated region, is an important risk factor for the development of thromboembolic disorders, especially in Caucasians. A number of methods are employed for clinical laboratory diagnosis of this mutation, some of which are capable of detecting adjacent 3'-end sequence variations. We present results from an African deep vein thrombosis patient tested for the 20210G --> A mutation by real-time polymerase chain reaction and melt-curve analysis using hybridization probes that incidentally detected an adjacent 3'-untranslated region variant. The patient sample was tested using the Factor II (Prothromobin) G20210A Kit (Roche Diagnostics, Indianapolis, Indiana, USA), in conjunction with the Roche LightCycler. A polymerase chain reaction fragment from the 3'-end of the F2 gene was subsequently sequenced for identification of the variant. Melt-curve analysis revealed a normal 20210*G peak and an unknown aberrant allelic peak. Following sequence analysis, the patient was determined to be heterozygous for 20209C --> T. The presence of the 20209C --> T variant in the current patient and in eight other reported individuals of African descent, most with thrombosis-associated complaints, suggests that this rare variant poses a potential increased risk for thromboembolic disease in this ethnic group.

Adult↗
PubMed2002

Peptide delivery to tissues via reversibly linked protein transduction sequences.

The development of peptide-based therapeutics has suffered from challenges associated with delivery to intact tissue. In skin, an array of protein targets resides only tens of micrometers below the surface; however, because of difficulties in traversing the cutaneous barrier, the potentialfor peptide-based therapeutics remains unrealized. We have developed a general approach for topical peptide delivery into skin using releasable protein transduction sequences to enable peptide transport across tissue boundaries. Upon entry into the cell, the disulfide linkage between the peptide transduction sequences and peptide cargo is cleaved, permitting the dissociation of the highly charged peptide transduction sequences from the active peptide. A protype cargo peptide, the hemagglutinin (HA) epitope, was conjugated to a hepta-arginine protein transduction sequence via a releasable disulfide linkage. This construct penetrated the skin to deep dermis within 1 h after topical application. Consistent with the dissociation of the protein transduction and cargo sequences, absorbed protein transduction sequences and HA peptides displayed differential intracellular localization. Reversible protein transduction sequence linkage thus represents a noninvasive platform for tissue delivery of intact peptides with no requirement for viral vectors or parenteral injection and may be of broad utility in molecular therapy.

Administration, Cutaneous↗
PubMed1996

The phylogenetic position and ultrastructure of the uncultured bacterium Achromatium oxaliferum.

Achromatium oxaliferum is a large, morphologically conspicuous, sediment-dwelling bacterium. Nothing is known concerning its phylogeny and it has eluded all attempts at laboratory cultivation. The limited physiological description of A. oxaliferum has been based on morphological features of the bacterium such as the presence of intracellular sulphur inclusions. A. oxaliferum cells were purified from a wetland region close to Rydal Water (Cumbria, UK). Scanning and transmission electron microscopy revealed that a number of morphologically distinct A. oxaliferum cell-types, based on cell surface features and the size and abundance of calcite and sulphur inclusions within the cells, were present in a single sample of purified cells. PCR was used to amplify almost full-length 16S rRNA gene sequences from DNA extracted from A. oxaliferum cells directly purified from sediments. The PCR products were cloned and partial sequences (approx. 400 bp) were determined for seven of the clones. Three different sequence clusters were recovered from the clone libraries. A near full-length (1489 bp) 16S rRNA gene sequence was determined for a representative clone of the most dominant sequence-type (52% of the sequences). Comparative sequence analysis showed A. oxaliferum to form a deep branching lineage within the gamma-subdivision of the Proteobacteria. A. oxaliferum was related most closely to the Chromatium assemblage that includes sulphur-oxidizing symbiotic bacteria, purple sulphur bacteria, and sulphur- and iron-oxidizing thiobacilli. Phylogenetic inferences made using distance, parsimony and maximum likelihood methods all placed A. oxaliferum with this group of bacteria. Bootstrap support for a relationship with any particular lineage within the assemblage was weak. The seven clone sequences recovered from the A. oxaliferum cells however formed a monophyletic group well supported by bootstrap analysis (85-100% support depending on the analysis done). It was concluded that A. oxaliferum was related to organisms of the Chromatium assemblage but constituted a novel lineage within this group of bacteria. A. oxaliferum cells were confirmed as the source of the 16S rRNA sequence obtained, by the use of a fluorescently-labelled 16S rRNA-targeted oligonucleotide specific for the A. oxaliferum rRNA sequence.

Base Sequence↗
PubMed2002

Structure and regulation of the omega-3 polyunsaturated fatty acid synthase genes from the deep-sea bacterium Photobacterium profundum strain SS9.

Omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (20:5n-3; EPA) and docosahexaenoic acid (22:6n-3; DHA) have been shown to be of major importance in the promotion of cardiovascular health, proper human development and the prevention of some cancers. A high proportion of bacterial isolates from low-temperature and high-pressure marine environments produce EPA or DHA. This paper presents the sequence of a 33 kbp locus from the deep-sea bacterium Photobacterium profundum strain SS9 which includes four of the five genes required for EPA biosynthesis. As with other bacterial pfa (polyunsaturated fatty acid) genes, the deduced amino acid sequences encoded by the SS9 genes reveal large multidomain proteins that are likely to catalyse EPA biosynthesis by a novel polyketide synthesis mechanism. RNase protection experiments separated the SS9 pfa genes into two transcriptional units, pfaA-C and pfaD. The pfaA transcriptional start site was identified. Cultivation at elevated hydrostatic pressure or reduced temperature did not increase pfa gene expression despite the resulting increase in percentage composition of EPA under these conditions. However, a regulatory mutant was characterized which showed both increased expression of pfaA-D and elevated EPA percentage composition. This result suggests that a regulatory factor exists which coordinates pfaA-D transcription. Additional consideration regarding the activities required for PUFA synthesis is provided together with comparative analyses of bacterial pfa genes and gene products.

Base Sequence↗
PubMed2005

Resolving deep phylogenetic relationships in salamanders: analyses of mitochondrial and nuclear genomic data.

Phylogenetic relationships among salamander families illustrate analytical challenges inherent to inferring phylogenies in which terminal branches are temporally very long relative to internal branches. We present new mitochondrial DNA sequences, approximately 2,100 base pairs from the genes encoding ND1, ND2, COI, and the intervening tRNA genes for 34 species representing all 10 salamander families, to examine these relationships. Parsimony analysis of these mtDNA sequences supports monophyly of all families except Proteidae, but yields a tree largely unresolved with respect to interfamilial relationships and the phylogenetic positions of the proteid genera Necturus and Proteus. In contrast, Bayesian and maximum-likelihood analyses of the mtDNA data produce a topology concordant with phylogenetic results from nuclear-encoded rRNA sequences, and they statistically reject monophyly of the internally fertilizing salamanders, suborder Salamandroidea. Phylogenetic simulations based on our mitochondrial DNA sequences reveal that Bayesian analyses outperform parsimony in reconstructing short branches located deep in the phylogenetic history of a taxon. However, phylogenetic conflicts between our results and a recent analysis of nuclear RAG-1 gene sequences suggest that statistical rejection of a monophyletic Salamandroidea by Bayesian analyses of our mitochondrial genomic data is probably erroneous. Bayesian and likelihood-based analyses may overestimate phylogenetic precision when estimating short branches located deep in a phylogeny from data showing substitutional saturation; an analysis of nucleotide substitutions indicates that these methods may be overly sensitive to a relatively small number of sites that show substitutions judged uncommon by the favored evolutionary model.

Animals↗
PubMed2025

Deep learning-based annotation of plant abiotic stress resistance genes for crops.

The declining costs of DNA sequencing have expanded genomic data, crucial for understanding plant abiotic stress responses and crop improvement. However, accurate gene annotation remains challenging. To address this limitation, we propose the PASRGA, a deep learning approach that leverages transfer learning and contrastive learning to annotate genes related to drought, salt, cold, and UV resistance. PASRGA achieves high F1-scores, area under the receiver operating characteristic (AUROC), area under the precision-recall curve (AUPRC), and Matthews correlation coefficient (MCC) in annotating stress resistance genes, significantly outperforming the general protein annotation model CLEAN, the plant phosphatase gene annotation model PF-NET, the top-ranked model in the CAFA5 challenge NetGO 4.0, and four traditional machine learning methods. Its effectiveness was further validated with a salt stress treatment experiment in Eutrema salsugineum. To facilitate crop breeding practices, we utilized PASRGA to annotate the genomes of 17 major crops. To improve accessibility and utility, we incorporated both manually curated and PASRGA-predicted gene data, together with the PASRGA tool, into the PlantASRG database (https://bioinfor.nefu.edu.cn/PlantASRG/). This comprehensive resource aims to support crop breeding initiatives and ensure food security.

Crops, Agricultural↗
PubMedDate not supplied

Complete nucleotide sequence of Japanese flounder (Paralichthys olivaceus) mitochondrial genome: structural properties and cue for resolving teleostean relationships.

We cloned and sequenced the complete mitochondrial genome of Japanese flounder (Paralichthys olivaceus). A circular 17,090 bp mitochondrial genome from the flounder contains 37 structural genes as in other vertebrates so far reported. This is the first report of the complete mitochondrial sequence from a higher teleostean fish (Acanthopterygii). The organization including gene order is quite similar to that of other teleostean fishes as well as placental mammals. The putative control region of the Japanese flounder mitochondrial genome contains a length variable region of about a 74 bp tandem repeat cluster. As a preliminary study we adopted the maximum likelihood and neighbor-joining inference methods to examine phylogenetic relationships among teleostean and related fishes. Comparisons of amino acid sequences of protein-coding genes and nucleotide sequences of tRNA genes resolved some middle to deep branches among some teleostean fishes. The flounder mitochondrial genome does not show an indication of evolutionary rate difference among teleosts leading to difficulty in phylogenetic analyses, and our data is useful for future evolutionary studies dealing with higher teleostean fishes.

Animals↗
PubMed2005

Extreme mtDNA divergences in a terrestrial slug (Gastropoda, Pulmonata, Arionidae): accelerated evolution, allopatric divergence and secondary contact.

Extremely high levels of intraspecific mtDNA differences in pulmonate gastropods have been reported repeatedly and several hypotheses to explain them have been postulated. We studied the phylogeny and phylogeography of 51 populations (n = 843) of the highly polymorphic terrestrial slug Arion subfuscus (Draparnaud, 1805) across its native distribution range in Western Europe. By combining the analysis of single stranded conformation polymorphisms (SSCP) and nucleotide sequencing, we obtained individual sequence data for a fragment of the mitochondrial 16S rDNA and a fragment of the nuclear ITS1. Additionally, five polymorphic allozyme loci were scored. Based on the 16S rDNA phylogeny, five monophyletic haplotype groups with sequence divergences of 9-21% were found. Despite this deep mitochondrial divergence, the haplotype groups were not monophyletic for the nuclear ITS1 fragment and haplotype group-specific allozyme alleles were not found. Although there is evidence for an accelerated mtDNA clock, the divergence among the haplotype groups is older than the Pleistocene and their current allopatric ranges probably reflect allopatric divergence and glacial survival in separate refugia from which different post-glacial colonization routes were established. A range-overlap of two mtDNA groups (S1 and S2, 21% sequence divergence) stretched from Central France and Belgium up to the North of the British Isles. The nuclear data suggest that this secondary contact resulted in hybridization between the allopatrically diverged groups. Therefore, it seems that, at least for two of the groups, the deep mtDNA divergence was only partially accompanied by the formation of reproductive isolation.

Animals↗
PubMed2000

Novel bacterial and archaeal lineages from an in situ growth chamber deployed at a Mid-Atlantic Ridge hydrothermal vent.

The phylogenetic diversity was determined for a microbial community obtained from an in situ growth chamber placed on a deep-sea hydrothermal vent on the Mid-Atlantic Ridge (23 degrees 22' N, 44 degrees 57' W). The chamber was deployed for 5 days, and the temperature within the chamber gradually decreased from 70 to 20 degrees C. Upon retrieval of the chamber, the DNA was extracted and the small-subunit rRNA genes (16S rDNA) were amplified by PCR using primers specific for the Archaea or Bacteria domain and cloned. Unique rDNA sequences were identified by restriction fragment length polymorphisms, and 38 different archaeal and bacterial phylotypes were identified from the 85 clones screened. The majority of the archaeal sequences were affiliated with the Thermococcales (71%) and Archaeoglobales (22%) orders. A sequence belonging to the Thermoplasmales confirms that thermoacidophiles may have escaped enrichment culturing attempts of deep-sea hydrothermal vent samples. Additional sequences that represented deeply rooted lineages in the low-temperature eurarchaeal (marine group II) and crenarchaeal clades were obtained. The majority of the bacterial sequences obtained were restricted to the Aquificales (18%), the epsilon subclass of the Proteobacteria (epsilon-Proteobacteria) (40%), and the genus Desulfurobacterium (25%). Most of the clones (28%) were confined to a monophyletic clade within the epsilon-Proteobacteria with no known close relatives. The prevalence of clones related to thermophilic microbes that use hydrogen as an electron donor and sulfur compounds (S(0), SO(4), thiosulfate) indicates the importance of hydrogen oxidation and sulfur metabolism at deep-sea hydrothermal vents. The presence of sequences that are related to sequences from hyperthermophiles, moderate thermophiles, and mesophiles suggests that the diversity obtained from this analysis may reflect the microbial succession that occurred in response to the shift in temperature and possible associated changes in the chemistry of the hydrothermal fluid.

Archaea↗
PubMed2000

Cryptic genetic variation and paraphyly in ravens.

Widespread species that are morphologically uniform may be likely to harbour cryptic genetic variation. Common ravens (Corvus corax) have an extensive range covering nearly the entire Northern Hemisphere, but show little discrete phenotypic variation. We obtained tissue samples from throughout much of this range and collected mitochondrial sequence and nuclear microsatellite data. Our study revealed a deep genetic break between ravens from the western United States and ravens from throughout the rest of the world. These two groups, the 'California clade' and the 'Holarctic clade' are well supported and over 4% divergent in mitochondrial coding sequence. Microsatellites also reveal significant differentiation between these two groups. Ravens from Minnesota, Maine and Alaska are more similar to ravens from Asia and Europe than they are to ravens from California. The two clades come in contact over a huge area of the western United States, with mixtures of the two mitochondrial groups present in Washington, Idaho and California. In addition, the restricted range Chihuahuan raven (Corvus cryptoleucus) of the south-west United States and Mexico is genetically nested within the paraphyletic common raven. Our findings suggest that the common raven may have formerly consisted of two allopatric groups that may be in the process of remerging.

Animals↗
PubMed2026

EvoSNR-Prom: Predicting promoters at single-nucleotide resolution with label-aware transfer learning of the pretrained EVO model.

The precise identification of promoters is crucial for understanding gene regulation. Deep learning methods have achieved considerable success in promoter prediction, yet most operate at the sequence level with coarse-grained labels. This means they label an entire DNA segment as either a "promoter" or "non-promoter," which results in a lack of the nucleotide-level resolution in prediction. In this study, we propose EvoSNR-Prom, a model designed for promoter prediction at single-nucleotide resolution. EvoSNR-Prom is built on the Evo foundation model and formulates promoter identification as a token-level sequence labeling problem, analogous to named entity recognition in natural language processing. To address the limited contextual information available in single-nucleotide tokenization, we introduce a lexicon-enhanced embedding strategy that incorporates biologically meaningful DNA lexicons, enriching contextual representations and improving the model's ability to capture complex sequence motifs. Furthermore, to enhance predictive performance on small size datasets, we integrate a label-aware transfer learning framework to leverage knowledge from well-annotated source species to a target organism. The results across various prokaryotic datasets show that EvoSNR-Prom achieves excellent performance. This work provides a valuable computational framework for the high-precision analysis of gene regulatory elements, contributing to the advancement of promoter prediction at single-nucleotide resolution.

Promoter Regions, Genetic↗
PubMed2007

Diversity and abundance of sulfate-reducing microorganisms in the sulfate and methane zones of a marine sediment, Black Sea.

The Black Sea, with its highly sulfidic water column, is the largest anoxic basin in the world. Within its sediments, the mineralization of organic matter occurs essentially through sulfate reduction and methanogenesis. In this study, the sulfate-reducing community was investigated in order to understand how these microorganisms are distributed relative to the chemical zonation: in the upper sulfate zone, at the sulfate-methane transition zone, and deeply within the methane zone. Total bacteria were quantified by real-time PCR of 16S rRNA genes whereas sulfate-reducing microorganisms (SRM) were quantified by targeting their metabolic key gene, the dissimilatory (bi)sulfite reductase (dsrA). Sulfate-reducing microorganisms were predominant in the sulfate zone but occurred also in the methane zone, relative proportion was maximal around the sulfate-methane transition, c. 30%, and equally high in the sulfate and methane zones, 5-10%. The dsrAB clone library from the sulfate-methane transition zone, showed mostly sequences affiliated with the Desulfobacteraceae. While, the dsrAB clone libraries from the upper, sulfate-rich zone and the deep, sulfate-poor zone were dominated by similar, novel deeply branching sequences which might represent Gram-positive spore-forming sulfate- and/or sulfite-reducing microorganisms. We thus hypothesize that terminal carbon mineralization in surface sediments of the Black Sea is largely due to the sulfate reduction activity of previously hidden SRM. Although these novel SRM were also abundant in sulfate-poor, methanogenic areas of the Black Sea sediment, their activities and possibly very versatile metabolic capabilities remain subject of further study.

Colony Count, Microbial↗
PubMed2004

[Magnetic resonance imaging in the diagnosis of benign and malignant pelvic tumors].

Magnetic resonance imaging (MRI) is an accepted imaging method for diagnosing diseases of the female pelvis. This review article describes the role of MR imaging for the diagnosis of benign and malignant pelvic tumors. Sagittal T2-weighted fast spin echo sequences can be effectively applied to diagnose leiomyomas of the uterus and provide exact pretreatment measurements of size and localization. In the diagnostic work-up of endometrial carcinoma, fat-saturated, T1-weighted gradient echo sequences make it possible to determine precisely how deep myometrial infiltration extends and what tissue should be included in preoperative treatment planning. In cervical cancer staging, MRI permits both assessment of local tumor extent and determination of tumor volume for planning and monitoring radiotherapy. The usefulness of MRI in cervical cancer staging is, however, limited since not all early-stage cancer (FIGO stage IA and small stage IB tumors) can be detected. Hence, it appears that the use of MRI as a screening method for cervical cancer cannot be recommended. MRI can distinguish between benign and malignant ovarian tumors with high sensitivity and specificity. Standard and fat-saturated T1-weighted sequences usually can diagnose teratomas with a specificity of 100 %. Axial fat-saturated, contrast enhanced T1-weighted spin echo sequences are useful in the staging of malignant ovarian tumors since they facilitate evaluation of their internal structure and will disclose peritoneal metastases. Besides staging of ovarian cancer, MRI can be applied for localization and for monitoring treatment response.

Adnexal Diseases↗
PubMed2003

Phylogenetic position of a deep-sea ascidian, Megalodicopia hians, inferred from the molecular data.

Ascidians inhabit both shallow water and the deep sea. The phylogenetic position of deep-sea ascidians has not been sufficiently investigated because of their unusual habitats. The family Octacnemidae is one such enigmatic deep-sea ascidian. In this report, we determined the sequences of the 18SrDNA and a mitochondrial protein gene of Megalodicopia hians belonging to the family Octacnemidae, and we analyzed its phylogenetic relationship with other ascidians. A phylogenetic relationship of this family with the families Cionidae and/or Corellidae has been suspected based on a small number of morphological characteristics. However, our results suggested that M. hians has a close relationship to the family Corellidae and might originate from them. This is the first report of the molecular phylogenetic analysis of a deep-sea ascidian.

Animals↗
PubMed2004

Molecular phylogeny of Zygomycota based on EF-1alpha and RPB1 sequences: limitations and utility of alternative markers to rDNA.

Earlier molecular phylogenetic analyses based on nuclear small subunit ribosomal DNA (nSSU rDNA) suggest that the Zygomycota are polyphyletic within the Chytridiomycota. However, these analyses failed to resolve almost all interordinal relationships among basal fungi (Chytridiomycota and Zygomycota), due to lack of sufficient characters within the nSSU rDNA. To further elucidate the higher-level phylogeny of Zygomycota, we have sequenced partial RPB1 (DNA dependent RNA polymerase II largest subunit) and EF-1alpha (translation elongation factor 1 alpha) genes from 10 and 3 zygomycete fungi, respectively. Independent molecular phylogenetic analyses were performed based on each sequence by distance and maximum likelihood methods. Although deep phylogenetic relationships among basal fungi still remain poorly resolved using either gene, the RPB1-based phylogeny identified a novel monophyletic clade consisting of the Dimargaritales, Harpellales, and Kickxellales. This result suggests that regularly formed septa (cross walls that divide hyphae into segments) with a lenticular cavity are plesiomorphic for this clade, and indicates the importance of septal pore ultrastructure in zygomycete phylogeny. In addition, a peculiar mucoralean genus Mortierella, which was considered to be distantly related to the other Mucorales based on previous nSSU rDNA analyses, was resolved as the basal most divergence within the Mucorales, consistent with traditional phenotypic-based taxonomy. Although the taxa included in our analysis are restricted, the monophyly of each order suggested by nSSU rDNA phylogeny is supported by the present RPB1-based analysis. These results support the potential use of RPB1 as an alternative marker for fungal phylogenetic studies. Conversely, the overall fungal phylogeny based on EF-1alpha sequence is poorly resolved. A comparison of numbers of observed substitutions versus inferred substitutions within EF-1alpha indicates that this gene is much more saturated than RPB1. This result suggests that the EF-1alpha gene is unsuitable for resolving higher-level phylogenetic relationships within the Fungi.

Animals↗
PubMed1980

Development of the brain stem in the rat. IV. Thymidine-radiographic study of the time of origin of neurons in the pontine region.

Groups of pregnant rats were injected with two successive daily doses of 3H-thymidine from gestational day 12 and 13 (E12 + 13) until the day before parturition (E21 + 22) in order to label in their embryos the proliferating precursors of neurons. At 60 days of age the proportion of neurons generated (or no longer labeled) on specific embryonic days was determined quantitatively in 14 nuclei of the pontine region. Peak production time of neurons of the trigeminal mesencephalic nucleus was on day E11 or earlier, with a small proportion generated on day E12. Peak production time of the trigeminal motor neurons was on day E12, with a small proportion produced earlier. Neurons of the principal sensory nucleus were generated between days E13 and E16, with a peak on day E14; the late-produced neurons tended to belong to a class of intermediate and large cells. The bulk of the neurons of the supratrigeminal and infratrigeminal nuclei arose on days E15 and E16. Neurons of the locus coeruleus are produced mostly on day E12, with about 20% of the cells arising on day E13. The bulk of the neurons of the dorsal tegmental nucleus (Gudden's) are produced between days E13 and E15, whereas most of the neurons of the deep (ventral) tegmental nucleus are produced on day E15. A dorsal-to-caudal gradient was also obtained between the dorsal and ventral nuclei of the lateral lemniscus, the neurons of the former being generated between days E12 and E15; the latter, between days E13 and E17. The neurons of both the pars lateralis and the pars medialis of the parabrachial nucleus were produced simultaneously between days E13 and E15, with a peak on day E13. The heterogeneous collection of neurons of the pontine paramedial reticular formation was produced for day E11 (or earlier) until day E15. Finally, the neurons of the raphe pontis parvicellularis were generated at an even rate between days E13 and E15, whereas the bulk of the neurons of the raphe pontis magnocellularis were produced on days E15 and E16. On the basis of datings obtained for 9 subdivisions of the entire brain stem trigeminal complex, hypotheses were offered of the cytogenetic components of the system. The sequence of neuron production in the dorsal and deep tegmental nuclei was related to their connections with divisions of the mammillary and habenular nuclei on a "first come-first serve" basis.

Animals↗