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Biology subjects

Kirkman, M.

Publications and source records attributed to Kirkman, M..

2 recordsLinked to original sources

Graded FGF activity patterns distinct cell types within the apical sensory organ of the sea anemone Nematostella vectensis

Bilaterian animals have evolved complex sensory organs comprised of distinct cell types that function coordinately to sense the environment. Each sensory unit has a defined architecture built from component cell types, including sensory cells, non-sensory support cells, and dedicated sensory neurons. Whether this characteristic cellular composition is present in the sensory organs of non-bilaterian animals is unknown. Here, we interrogate the cell type composition and gene regulatory networks controlling development of the larval apical sensory organ in the sea anemone Nematostella vectensis. Using single cell RNA sequencing and imaging approaches, we reveal two unique cell types in the Nematostella apical sensory organ, GABAergic sensory cells and a putative non-sensory support cell population. Further, we identify the paired-like (PRD) homeodomain gene prd146 as a specific sensory cell marker and show that Prd146+ sensory cells become post-mitotic after gastrulation. Genetic loss of function approaches show that Prd146 is essential for apical sensory organ development. Using a candidate gene knockdown approach, we place prd146 downstream of FGF signaling in the apical sensory organ gene regulatory network. Further, we demonstrate that an aboral FGF activity gradient coordinately regulates the specification of both sensory and support cells. Collectively, these experiments define the genetic basis for apical sensory organ development in a non-bilaterian animal and reveal an unanticipated degree of complexity in a prototypic sensory structure.

developmental biology↗

rRNA transcription is integral to liquid-liquid phase separation and maintenance of nucleolar structure

Beginning with transcription of ribosomal RNA (rRNA) by RNA Polymerase (Pol) I in the nucleolus, ribosome biogenesis is intimately tied to cell growth and proliferation. Perturbation of ribosome biogenesis has been previously shown to affect nucleolar structure, yet the underlying mechanism is unknown. We generated loss-of-function mouse mutants of Pol I subunits, Polr1a, Polr1b, Polr1c and Polr1d, thereby genetically inhibiting rRNA transcription and ribosome biogenesis. Pol I mutant embryos are preimplantation lethal and have fewer nucleoli. Using hiPSCs triple labeled for the three nucleolar compartments, we observe two phenotypes upon Pol I inhibition: a single condensed nucleolus, and fragmented nucleoli. We find that when rRNA transcription is inhibited, the viscosity of the granular compartment of the nucleolus is increased disrupting its liquid-liquid phase separation properties, which results in a condensed nucleolus. Taken together, our data suggests that Pol I function and rRNA transcription are required for maintaining nucleolar structure and integrity.

developmental biology↗