Biology subjects

Lee, J.-R.

Publications and source records attributed to Lee, J.-R..

4 recordsLinked to original sources

bioRxiv2024

Deep homology of a brachyury regulatory syntax and origin of the notochord

The brachyury gene encodes a T-box transcription factor (TF) that is crucial for the development of the notochord, a novel trait of chordates1. Brachyury expression in axial mesodermal cells (notochord progenitors) is regarded as a chordate innovation2, yet it remains unclear how the chordate ancestor acquired this expression domain. By examining the sequences of previously identified notochord enhancers of several chordate brachyury genes3-5, we uncovered a regulatory syntax consisting of binding sites for four TFs (Su(H), Foxh1, Zic, and Ets) with a strict order and orientation. We also identified this syntax, here named SFZE, in potential cis-regulatory modules (CRMs) of brachyury orthologs in various non-chordate animals and even in Capsaspora, a close unicellular relative to animals. Reporter assays demonstrated that SFZE-containing CRMs from non-chordate organisms exhibited regulatory activity in the zebrafish notochord, and mutagenesis of the TF sites reduced the activity. Furthermore, the SFZE syntax in sea urchin confers its endoderm activity, with the TF sites functionally decoupled during gastrulation. These findings indicate that the association of the SFZE syntax with brachyury is ancient, likely predating the origin of animals. The emergence of axial brachyury expression is therefore probably not the result of a newly acquired notochord enhancer, but is instead likely attributed to co-option of upstream signals acting on the conserved SFZE syntax, which facilitates the origin of the notochord from rudimentary endodermal cells.

evolutionary biology↗

bioRxiv2024

Transgenesis enables mapping of segmental ganglia in the leech Helobdella austinensis

The analysis of how neural circuits function in individuals and change during evolution is simplified by the existence of neurons identified as homologous within and across species. Invertebrates, including leeches, have been used for these purposes in part because their nervous systems comprise a high proportion of identified neurons, but technical limitations make it challenging to assess the full extent to which assumptions of stereotypy hold true. Here, we introduce Minos plasmid-mediated transgenesis as a tool for introducing transgenes into the embryos of the leech Helobdella austinensis (Spiralia; Lophotrochozoa; Annelida; Clitellata; Hirudinida; Glossiphoniidae). We identified an enhancer driving pan-neuronal expression of markers, including histone2B:mCherry, which allowed us to enumerate neurons in segmental ganglia. Unexpectedly, we find that adult Helobdella ganglia contain fewer and more variable numbers of neurons than in previously examined leech species.

zoology↗

bioRxiv2023

Epidermal turnover in the planarian Schmidtea mediterranea involves basal cell extrusion and intestinal digestion.

Planarian flatworms undergo continuous internal turnover, wherein old cells are replaced by the division progeny of adult pluripotent stem cells known as neoblasts. How dynamic cell turnover is executed at the organismal scale remains an intriguing question in planarians and biological systems in general. While previous studies have predominantly focused on neoblast proliferation, little is known about the processes that mediate cell loss during tissue homeostasis. Here, we use the planarian epidermis as a model to study the mechanisms of cell removal in Schmidtea mediterranea. We established a covalent dye-labeling assay and image analysis pipeline to quantify the cell turnover rate in the planarian epidermis. Our findings indicate that the ventral epidermis is highly dynamic, with a half-life of the constituent cells of approximately 4.5 days. Using live-imaging and pulse-chase assays, we find that epidermal cells undergo internalization via basal extrusion, followed by a migration towards the intestine and ultimately digestion by intestinal phagocytes. Overall, our studies reveal an intricate homeostatic cell clearance process that may reduce the metabolic costs of high turnover tissues in planarians.

developmental biology↗

bioRxiv2019

Heterochronically expressed midline netrin was recruited to guide mesoderm migration in epibolic gastrulation of the leech

Netrin is a remarkably conserved midline landmark, serving as a chemotactic factor that organizes the bilateral neural architecture in the post-gastrula bilaterian embryos. Netrin signal also guides cell migration in many other neural and non-neural organogenesis events in later developmental stages, but it has never been before found to participate in gastrulation - the earliest cell migration in metazoan embryogenesis. Here, we found that netrin signaling molecules and their receptors are expressed during gastrulation of the leech Helobdella. Intriguigly, Hau-netrin-1 was expressed in the N lineage, the precursor of ventral ectoderm, at the onset of gastrulation. We demonstrated that the N lineage is required for the entrance of mesoderm into the germinal band and that misexpression of Hau-netrin-1 in early gastrulation prevented mesoderm from entering the germinal band. Together, these results suggested that Hau-netrin-1 secreted by the N lineage guides mesoderm migration during germinal band assembly. Furthermore, ectopic expression of Hau-netrin-1 after the completion of germinal band assembly disrupted the epibolic migration of the germinal bands in a later stage of gastrulation. Thus, Hau-netrin-1 is likely involved in two distinct events in sequential stages of leech gastrulation: the assembly of germinal bands in early gastrulation and their epibolic migration in mid-gastrulation. This mode of gastrulation as observed in the leech is apomorphic for clitellate annelids. We postulated that a heterochronic shift of netrin gene expression in the clitellate ancestor might have facilitated the evolutionary emergence of a novel form of gastrulation in this lineage.

developmental biology↗