Biology subjects

Gahan, J. M.

Publications and source records attributed to Gahan, J. M..

4 recordsLinked to original sources

bioRxiv2021

The chromatin-regulating CoREST complex is animal specific and essential for development in the cnidarian Nematostella vectensis

Chromatin-modifying proteins are key players in the regulation of development and cell differentiation in animals. Many individual chromatin modifiers, however, predate the evolution of animal multicellularity and how they became integrated into the regulatory networks underlying development is unclear. Here we show that CoREST is an animal-specific protein that assembles a conserved, vertebrate-like histone-modifying complex including Lsd1 and HDAC1/2 in the sea anemone Nematostella vectensis. We further show that NvCoREST expression overlaps fully with that of NvLsd1 throughout development. NvCoREST mutants, generated using CRISPR-Cas9, reveal essential roles during development and for the differentiation of cnidocytes, thereby phenocopying NvLsd1 mutants. We also show that this requirement is cell autonomous using a cell-type-specific rescue approach. Together, this shows that the evolution of CoREST allowed the formation of a chromatin-modifying complex that was present before the last common cnidarian-bilaterian ancestor and thus represents an ancient component of the animal developmental toolkit.

evolutionary biology↗

bioRxiv2021

Insm1-expressing neurons and secretory cells develop from a common pool of progenitors in the sea anemone Nematostella vectensis

Neurons are highly specialized cells present in nearly all animals, but their evolutionary origin and relationship to other cell types is not well understood. We use here the sea anemone Nematostella vectensis as a model system for early-branching animals to gain fresh insights into the evolutionary history of neurons. We generated a transgenic reporter line to show that the transcription factor NvInsm1 is expressed in post-mitotic cells that give rise to various types of neurons and secretory cells. Expression analyses, double transgenics and gene knockdown experiments show that the NvInsm1-expressing neurons and secretory cells derive from a common pool of NvSoxB(2)-positive progenitor cells. These findings, together with the requirement for Insm1 for the development of neurons and endocrine cells in vertebrates, support a close evolutionary relationship of neurons and secretory cells.

developmental biology↗

bioRxiv2020

Histone demethylase Lsd1 is required for the differentiation of neural cells in the cnidarian Nematostella vectensis

The evolution of multicellularity was accompanied by the emergence of processes to regulate cell fate, identity and differentiation in a robust and faithful manner. Chromatin regulation has emerged as a key process in development and yet its contribution to the evolution of such processes is largely unexplored. Chromatin is regulated by a diverse set of proteins, which themselves are tightly regulated in order to play cell/ tissue-specific functions. Using the cnidarian Nematostella vectensis, a model for basal metazoans, we explore the function of one such chromatin regulator, Lysine specific demethylase 1 (Lsd1). We generated an endogenously tagged allele and show that the expression of NvLsd1 is developmentally regulated and higher in differentiated neural cells than their progenitors. We further show, using a CRISPR/Cas9 generated mutant that loss of NvLsd1 leads to several distinct developmental abnormalities. Strikingly, NvLsd1 loss leads to the almost complete loss of differentiated cnidocytes, cnidarian-specific neural cells, which we show to be the result of a cell-autonomous requirement for NvLsd1. Together this suggests that complex regulation of developmental processes by chromatin modifying proteins predates the split of the cnidarian and bilaterian lineages, approximately 600 million years ago, and may constitute an ancient feature of animal development.

developmental biology↗

bioRxiv2020

The genetic basis for PRC1 complex diversity emerged early in animal evolution

Polycomb group proteins are essential regulators of developmental processes across animals. Despite their importance, studies on Polycomb are often restricted to classical model systems and, as such, little is known about the evolution of these important chromatin regulators. Here we focus on Polycomb Repressive Complex 1 (PRC1) and trace the evolution of core components of canonical and non-canonical PRC1 complexes in animals. Previous work suggested that a major expansion in the number of PRC1 complexes occurred in the vertebrate lineage. Here we show that the expansion of the PCGF protein family, an essential step for the establishment of the large diversity of PRC1 complexes found in vertebrates, predates the bilaterian-cnidarian ancestor. This means that the genetic repertoire necessary to form all major vertebrate PRC1 complexes emerged early in animal evolution, over 550 million years ago. We further show that PCGF5, a gene conserved in cnidarians and vertebrates but lost in all other studied groups, is expressed in the nervous system in the sea anemone Nematostella vectensis, similar to its mammalian counterpart. Together this work provides an evolutionary framework to understand PRC1 complex diversity and evolution and establishes Nematostella as a promising model system in which this can be further explored.

evolutionary biology↗