Biology subjects

Drummer, C.

Publications and source records attributed to Drummer, C..

6 recordsLinked to original sources

bioRxiv2026

Coordinated neural progenitor adaptations drive primate neocortical downscaling

Most primates possess a large, highly folded (gyrencephalic) neocortex, a feature present in the primate common ancestor. In contrast, several New World monkey species display a comparatively small and largely smooth, unfolded (lissencephalic) neocortex. One prominent example is the common marmoset, an increasingly popular model in neuroscience. This phenotype likely reflects an evolutionary reduction from the ancestral primate condition, implying modifications in neurodevelopmental programs. One essential basis for neocortical development is the activity and behavior of neural progenitor cells (NPCs). Here, we identify coordinated adaptations in NPC biology that bias neurodevelopmental trajectories toward neocortical downscaling. By combining marmoset and human cerebral organoids with analyses of fetal marmoset neocortical tissue and previously published histological data, we uncover multiple adaptations in apical and basal progenitors that converge on reduced progenitor capacity, alter early progenitor dynamics, and likely constrain neuronal output, thereby limiting the size and folding of the marmoset neocortex.

evolutionary biology↗

bioRxiv2025

The evolution of gene regulatory programs controlling gonadal development in primates

Sex-determining pathways produce dimorphic gonads (ovaries and testes), yet the gene regulatory programs governing gonadogenesis and their evolution in primates remain little explored. Here we report evolutionary analyses of transcriptome and chromatin accessibility data of male and female human, marmoset (New World monkey), and mouse gonadal cells spanning key prenatal stages. We find that the two primates and mouse share similar X chromosome expression dynamics, including X chromosome reactivation (XCR), and that in Klinefelter syndrome (XXY) testes, germ cells undergo female-like XCR and escape of X inactivation. New male-specific regulatory regions have emerged progressively during mammalian evolution, especially on the X following sex chromosome origination. Further analyses revealed that male-specific regulatory regions evolved faster than female-specific ones in both supporting and pre-meiotic germ cells. However, female meiotic germ cells show even higher rates of molecular evolution and exhibit a permissive chromatin state that facilitates the birth of new genes, thus resembling their adult spermatogenic counterparts. Finally, we traced both conserved and species-specific gene expression trajectories across the three mammals, uncovering candidate genes for disorders of sex development that are typically central to cell-type-specific regulatory networks. Together, our study unveils both ancestral mammalian and recently evolved gene regulatory programs that control human- and primate-specific aspects of gonadal development in both sexes.

evolutionary biology↗

bioRxiv2025

The evolution of gene regulation in mammalian cerebellum development

Gene regulatory changes are considered major drivers of evolutionary innovations, including the cerebellums expansion during human evolution, yet they remain largely unexplored. In this study, we combined single-nucleus measurements of gene expression and chromatin accessibility from six mammals (human, bonobo, macaque, marmoset, mouse, and opossum) to uncover conserved and diverged regulatory networks in cerebellum development. We identified core regulators of cell identity and developed sequence-based models that revealed conserved regulatory codes. By predicting chromatin accessibility across 240 mammalian species, we reconstructed the evolutionary histories of human cis-regulatory elements, identifying sets associated with positive selection and gene expression changes, including the recent gain of THRB expression in cerebellar progenitor cells. Collectively, our work reveals the shared and mammalian lineage-specific regulatory programs governing cerebellum development.

evolutionary biology↗

bioRxiv2025

Neuronal cell adhesion molecule (NRCAM) variant defined by microexon skipping is an essential, antigenically distinct, and targetable surface proteoform in high-grade glioma

To overcome the paucity of known tumor-specific surface antigens in pediatric high-grade glioma (pHGG), we contrasted splicing patterns in pHGGs and normal brain samples. Among alternative splicing events affecting extracellular protein domains, the most pervasive alteration was the skipping of [≤]30 nucleotide-long exons. Several of these skipped microexons mapped to L1-IgCAM family members, such as NRCAM. Bulk and single-nuclei short- and long-read RNA-seq revealed uniform skipping of NRCAM microexons 5 and 19 in virtually every pHGG sample. Importantly, the {Delta}ex5{Delta}ex19 (but not the full-length) NRCAM proteoform was essential for pHGG cell migration and invasion in vitro and tumor growth in vivo. We developed a monoclonal antibody selective for {Delta}ex5{Delta}ex19 NRCAM and demonstrated that "painting" of pHGG cells with this antibody enables killing by T cells armed with an FcRI-based universal immune receptor. Thus, pHGG-specific NRCAM and possibly other L1-IgCAM proteoforms are promising and highly selective targets for adoptive immunotherapies.

cancer biology↗

bioRxiv2020

Cardiac MRI in common marmosets revealing age-dependency of cardiac function

The aim of this study was to establish a feasible and robust magnetic resonance imaging protocol for the quantitative assessment of cardiac function in marmosets and to present normal values of cardiac function across different ages from young adult, middle-aged, to very old clinically healthy animals.Cardiac MRI of 33 anesthetized marmosets at the age of 2-15 years was performed at 9.4 T using IntraGate-FLASH that operates without any ECG-triggering and breath holding. Normalized to post-mortem heart weight, the left ventricular end-diastolic volume (LV-EDV) was significantly reduced in older marmosets. The LV end-systolic volume (LV-ESV) and the LV stroke volume (LV-SV) showed a similar trend while the LV ejection fraction (LV-EF) and wall thickening remained unchanged. Similar observations were made for the right ventricle. Moreover, the total ventricular myocardial volume was lower in older monkeys while no significant difference in heart weight was found.In conclusion, IntraGate-FLASH allowed for quantification of left ventricular cardiac function but seems to underestimate the volumes of the right ventricle. Although less strong and without significant sex differences, the observed age related changes were similar to previously reported findings in humans supporting marmosets as a model system for age related cardiovascular human diseases.Competing Interest StatementThe authors have declared no competing interest.View Full Text

zoology↗

bioRxiv2019

Neolithic genomes reveal a distinct ancient HLA allele pool and population transformation in Europe

The Wartberg culture (WBC, 3,500-2,800 BCE) dates to the Late Neolithic period, a time of important demographic and cultural transformations in western Europe. We perform a genome-wide analysis of 42 individuals who were interred in a WBC collective burial in Niedertiefenbach, Germany (3,300-3,200 cal. BCE). Our results highlight that the Niedertiefenbach population indeed emerged at the beginning of the WBC. This farming community was genetically heterogeneous and carried a surprisingly large hunter-gatherer ancestry component (40%). We detect considerable differences in the human leukocyte antigen gene pool between contemporary Europeans and the Niedertiefenbach individuals whose immune response was primarily geared towards defending viral infections.

evolutionary biology↗