Biology subjects

Giere, P.

Publications and source records attributed to Giere, P..

3 recordsLinked to original sources

bioRxiv2021

Cellular development and evolution of the mammalian cerebellum

The expansion of the neocortex, one of the hallmarks of mammalian evolution1,2, was accompanied by an increase in the number of cerebellar neurons3. However, little is known about the evolution of the cellular programs underlying cerebellum development in mammals. In this study, we generated single-nucleus RNA-sequencing data for [~]400,000 cells to trace the development of the cerebellum from early neurogenesis to adulthood in human, mouse, and the marsupial opossum. Our cross-species analyses revealed that the cellular composition and differentiation dynamics throughout cerebellum development are largely conserved, except for human Purkinje cells. Global transcriptome profiles, conserved cell state markers, and gene expression trajectories across neuronal differentiation show that the cerebellar cell type-defining programs have been overall preserved for at least 160 million years. However, we also discovered differences. We identified 3,586 genes that either gained or lost expression in cerebellar cells in one of the species, and 541 genes that evolved new expression trajectories during neuronal differentiation. The potential functional relevance of these cross-species differences is highlighted by the diverged expression patterns of several human disease-associated genes. Altogether, our study reveals shared and lineage-specific programs governing the cellular development of the mammalian cerebellum, and expands our understanding of the evolution of mammalian organ development.

evolutionary biology↗

bioRxiv2021

Promoter repression and 3D-restructuring resolves divergent developmental gene expression in TADs

Cohesin loop extrusion facilitates precise gene expression by continuously driving promoters to sample all enhancers located within the same topologically-associated domain (TAD). However, many TADs contain multiple genes with divergent expression patterns, thereby indicating additional forces further refine how enhancer activities are utilised. Here, we unravel the mechanisms enabling a new gene, Rex1, to emerge with divergent expression within the ancient Fat1 TAD in placental mammals. We show that such divergent expression is not determined by a strict enhancer-promoter compatibility code, intra-TAD position or nuclear envelope-attachment. Instead, TAD-restructuring in embryonic stem cells (ESCs) separates Rex1 and Fat1 with distinct proximal enhancers that independently drive their expression. By contrast, in later embryonic tissues, DNA methylation renders the inactive Rex1 promoter profoundly unresponsive to Fat1 enhancers within the intact TAD. Combined, these features adapted an ancient regulatory landscape during evolution to support two entirely independent Rex1 and Fat1 expression programs. Thus, rather than operating only as rigid blocks of co-regulated genes, TAD-regulatory landscapes can orchestrate complex divergent expression patterns in evolution. HIGHLIGHTSO_LINew genes can emerge in evolution without taking on the expression pattern of their surrounding pre-existing TAD. C_LIO_LICompartmentalisation can restructure seemingly evolutionarily stable TADs to control a promoters access to enhancers. C_LIO_LILamina-associated domains neither prevent transcriptional activation nor enhancer-promoter communication. C_LIO_LIRepression rather than promoter-specificity refines when genes respond to promiscuous enhancer activities in specific tissues. C_LI

genetics↗

bioRxiv2021

Phenotyping in the era of genomics: MaTrics a digital character matrix to document mammalian phenotypic traits coded numerically

A new and uniquely structured matrix of mammalian phenotypes, MaTrics (Mammalian Traits for Comparative Genomics) is presented in a digital form. By focussing on mammalian species for which genome assemblies are available, MaTrics provides an interface between mammalogy and comparative genomics. MaTrics was developed as part of a project to link phenotypic differences between mammals to differences in their genomes using Forward Genomics. Apart from genomes this approach requires information on homologous phenotypes that are numerically encoded (presence-absence; multistate character coding*) in a matrix. MaTrics provides these data, links them to at least one reference (e.g., literature, photographs, histological sections, CT-scans, or museum specimens) and makes them available in a machine actionable NEXUS-format. By making the data computer readable, MatTrics opens a new way for digitizing collections. Currently, MaTrics covers 147 mammalian species and includes 207 characters referring to structure, morphology, physiology, ecology and ethology. Researching these traits revealed substantial knowledge gaps, highlighting the need for substantial phenotyping efforts in the genomic era. Using the trait information documented in MaTrics, previous Forward Genomics screens identified changes in genes that are associated with various phenotypes, ranging from fully-aquatic lifestyle to dietary specializations. These results motivate the continuous expansion of phenotype information, both by filling research gaps or by adding additional taxa and traits. MaTrics is digitally available online within the data repository Morph{middle dot}D{middle dot}Base (www.morphdbase.de).

zoology↗