Biology subjects

Klein, C. C.

Publications and source records attributed to Klein, C. C..

6 recordsLinked to original sources

bioRxiv2026

Distinct cortical networks associated with subregions of the hippocampal-entorhinal system in the first two years of human life

Episodic memory critically depends on the hippocampus and the entorhinal cortex. Despite a rapid developmental change in human episodic memory during the first two years of life, little is known about the developmental trajectory of the hippocampal-entorhinal circuitry during this critical time period. In the current study, we collected high-quality precision fMRI data from five typically developing infants over the time period between 1 and 2 years of life and examined, in great anatomical detail, the developmental profile of distinct parts of the infant hippocampal-entorhinal system and their coupling with distinct cortical networks. We show that already at around 1 year of age, subdivisions of the canonical default network (DN) are fully dissociated at the neocortex and are differently associated with the hippocampal-entorhinal system, with tentatively differential developmental trajectories. While the DN-A, associated with episodic simulation, coupled with the anterior hippocampus and the medial part of the entorhinal cortex, the DN-B, associated with social cognition, showed significantly weaker connectivity with the hippocampal-entorhinal system. Furthermore, the parietal memory network coupled with the posterior hippocampus and the lateral part of the entorhinal cortex. Exploratory longitudinal results suggest that associations of the DN-B with the hippocampus and the entorhinal cortex increase towards the end of the second postnatal year, and the associations of the parietal memory network become more topographically restricted to the posterior hippocampus. These networks and their differential maturation may provide the basis for important developments in episodic memory and social cognition in the second postnatal year and suggest that potentially unique properties of human hippocampal-entorhinal circuitry may emerge latest in development.

neuroscience↗

bioRxiv2025

Grammar acquisition in preschool children is related to white matter maturation of the dorsal language network

In preschool years, children take important steps in grammar acquisition, which are essential to learning their native language. A central aspect is the acquisition of the morpho-syntactic rule system, which forms an intersection between words and sentences. In adults, rule-based linguistic processes are supported by the dorsal fiber pathway to BA44, the arcuate fascicle. This pathway matures relatively late in development, raising the question of whether it already supports grammar processes in the early preschool years, or whether early grammar acquisition is supported by different, earlier-maturing fiber pathways. In two independent samples of 3- to 5-year-old children (N = 90 and N = 30), we examined the association between the maturation of fiber pathways of the language network and childrens noun plural assignment as an index of their morpho-syntactic abilities. This revealed consistent differences between 3-year-olds and 4- to 5-year-olds. The 4- and 5-year-olds, but not 3-year-olds, showed a relation of morpho-syntax with both the dorsal pathway to BA44, supporting syntactic processes, and the dorsal pathway to BA6, supporting phonological processes in adults. Our results suggest that, in contrast to adults, preschool-aged children rely on both dorsal fiber pathways for morpho-syntax. This difference might point to different processing strategies reflecting the transition from phonology-based statistical learning to rule-based learning in grammar acquisition.

developmental biology↗

bioRxiv2022

Children's syntax is supported by the maturation of BA44 at 4 years, but of the posterior STS at 3 years of age

Within the first years of life, children learn major aspects of their native language. However, the ability to process complex sentence structures, a core faculty in human language called syntax, has been found to emerge only slowly. A milestone in the acquisition of syntax is reached around the age of 4, when children learn a variety of syntactic concepts, including, for example, subordinate clauses. Here, we ask which maturational changes in the childs brain underlie the emergence of syntactic abilities around this critical age. We relate markers of cortical brain maturation to 3- and 4-year-olds syntactic in contrast to other language abilities. Our results show that distinct cortical brain areas support syntax in the two age groups: While 3-year-old childrens syntactic abilities were associated with increased surface area in the most posterior part of the left superior temporal sulcus, 4-year-old children showed an association with cortical thickness in the left posterior part of Brocas area, i.e. BA44. The present findings suggest that syntactic abilities rely on the maturation of distinct cortical regions in 3- compared to 4-year-olds. The observed shift to more mature regions involved in syntax may underlie the behavioral milestones in syntax acquisition around 4 years of age.

neuroscience↗

bioRxiv2022

A transcriptional program shared across lineages underlies cell differentiation during metazoan development

BackgroundDuring development, most cells undergo striking changes in order to develop into functional tissues. All along this process, the identity of each tissue arises from the particular combination of regulatory transcription factors that specifically control the expression of relevant genes for growth, pattern formation and differentiation. In this scenario, regulation of gene expression turns out to be essential to determine cell fate and tissue specificity. ResultsTo characterize the dynamic transcriptional profiles during cellular differentiation, we tracked down the transcriptome of committed cells in different Drosophila melanogaster tissues and compartments at a number of developmental stages. We found that during fly development, temporal transcriptional changes shared across lineages are much larger than spatial lineage-specific transcriptional changes, and that cellular differentiation is dominated by a transcriptional program, common to multiple lineages, that governs the transition from undifferentiated to fully differentiated cells independently from the differentiation end point. The program is under weak epigenetic regulation, and it is characterized by downregulation of genes associated with cell cycle, and concomitant activation of genes involved in oxidative metabolism. Largely orthogonal to this program, tissue specific transcriptional programs, defined by a comparatively small number of genes are responsible for lineage specification. Transcriptome comparisons with worm, mouse and human, reveal that this transcriptional differentiation program is broadly conserved within metazoans. ConclusionsOur data provides a novel perspective to metazoan development, and strongly suggest a model, in which the main transcriptional drive during cell type and tissue differentiation is the transition from precursor undifferentiated to terminally differentiated cells, irrespective of cell type.

genomics↗

bioRxiv2020

Dynamics of gene expression and chromatin marking during cell state transition

We have monitored the transcriptomic and epigenomic status of cells at twelve time-points during the transdifferentiation of human pre-B cells into macrophages. Using this data, we have investigated some fundamental questions regarding the role of chromatin in gene expression. We have found that, over time, genes are characterized by a limited number of chromatin states (combinations of histone modifications), and that, consistently, chromatin changes over genes tend to occur in a coordinated manner. We have observed strong association between these changes and gene expression only at the time of initial gene activation. Activation is preceded by H3K4me1 and H3K4me2, and followed in a precise order by most other histone modifications. Further changes in gene expression, comparable or even stronger than those at initial activation, occur without associated changes in histone modifications. The data generated here constitutes, thus, a unique resource to investigate transcriptomic and epigenomic dynamics during a differentiation process.

genomics↗

bioRxiv2019

bsAS, an antisense long non-coding RNA, controls cell fate through regulation of blistered/DSRF isoform expression

SummaryNatural Antisense Transcripts (NATs) are long non-coding RNAs (lncRNAs) that overlap coding genes in the opposite strand. NATs roles have been related to gene regulation through different mechanisms, including post-transcriptional RNA processing. With the aim to identify NATs with potential regulatory function during fly development, we generated RNA-Seq data in eye-antenna, leg, and wing at third instar larvae. Among the candidate NATs, we found bsAS, antisense to bs/DSRF, a gene involved in wing development and neural processes. Through the analysis of the RNA-Seq data, we found that these two different functions are carried out by the two different protein isoforms encoded in the bs gene. We also found that the usage of these isoforms is regulated by bsAS. This regulation is essential for the correct determination of cell fate during Drosophila development, as bsAS knockouts show highly aberrant phenotypes. bs regulation by bsAS is mediated by the specific physical interaction of the bsAS promoter with the promoters of bs, and it likely involves a mechanism, where expression of bsAS leads to the collision of RNA polymerases acting in opposite directions, preventing the elongation of the longer isoforms of bs, the ones carrying the neural related functions. Evolutionary analysis suggests that the bsAS NAT emerged simultaneously to the long-short isoform structure of bs, preceding the emergence of wings in insects, and maybe related to regulation of neural differentiation.

molecular biology↗