Biology subjects

Turnbaugh, E. M.

Publications and source records attributed to Turnbaugh, E. M..

3 recordsLinked to original sources

bioRxiv2025

Antibodies targeting HSV glycoprotein B require effector functions to protect neonatal mice

Glycoprotein B (gB) serves as the viral fusion protein for herpes simplex virus (HSV), mediating fusion between viral and host membranes resulting in infection. As such, gB represents a potentially critical target for the host immune system with high potential relevance for vaccine design. Here we investigated the mechanisms of protection for a panel of gB-specific monoclonal antibodies (mAb) in a mouse model of neonatal HSV (nHSV) infection. Viral neutralization contributed, but Fc effector functions were critical for mAb-mediated protection against nHSV mortality, depending on dose. Moreover, AAV-mediated in vivo expression of a gB-specific mAb in mice provided transgenerational protection against HSV-1 and HSV-2 mortality in their offspring. These findings demonstrate that antibodies targeting gB can serve as potent therapeutics and that they require diverse functional profiles to afford optimal protection, informing vaccine design.

immunology↗

bioRxiv2025

Her9 is required for the migration, differentiation, and survival of neural crest cells

Neural crest cells (NCC) are vertebrate-specific multipotent progenitor cells that arise from the neural plate border and go on to contribute to a wide variety of morphological structures such as the jaw and palate, enteric nervous system (ENS), and pigment cells. Defects in essential steps in neural crest cell development have been associated with a wide variety of congenital disorders, collectively referred to as neurocristopathies. Her9/Hes4 is a bHLH-O transcriptional repressor that has been shown to regulate neural crest cell and craniofacial development in Xenopus and zebrafish, however the extent of Her9 function in other neural crest cell lineages has not been investigated. In this study, we characterized NCC phenotypes in her9 mutant zebrafish. We show that loss of Her9 perturbs the development of several NCC derivatives. Her9 mutants display a variety of NCC defects, including craniofacial abnormalities, alterations in pigment cell lineages, and improper formation of the gut. These phenotypes are associated with defects in neural crest cell specification, migration, and differentiation, as well as an upregulation in expression of BMP ligand genes. Furthermore, loss of Her9 leads to apoptosis of NCC derivatives. Collectively, our results show that Her9 functions in neural crest development by regulating members of the NCC gene regulatory network (GRN) to control NCC specification, migration, differentiation and survival.

developmental biology↗

bioRxiv2019

Her9/HES4 is required for retinal photoreceptor development, maintenance, and survival

The intrinsic and extrinsic factors that regulate vertebrate photoreceptor specification and differentiation are complex, and our understanding of all the players is far from complete. Her9, the zebrafish ortholog of human HES4, is a basic helix-loop-helix-orange (bHLH-O) transcriptional repressor that regulates neurogenesis in several developmental contexts. We have previously shown that her9 is upregulated during chronic rod photoreceptor degeneration and regeneration in adult zebrafish, but little is known about the role of her9 during retinal development. To better understand the function of Her9 in the retina, we generated zebrafish her9 CRISPR mutants. Her9 homozygous mutants displayed striking retinal phenotypes, including decreased numbers of rods and red/green cones, whereas blue and UV cones were relatively unaffected. The reduction in rods and red/green cones correlated with defects in photoreceptor subtype lineage specification. The remaining rods and double cones displayed abnormally truncated outer segments, and elevated levels of apoptosis. In addition to the photoreceptor defects, her9 mutants also possessed a reduced proliferative ciliary marginal zone, and decreased and disorganized Muller glia. Mutation of her9 was larval lethal, with no mutants surviving past 13 days post fertilization. Our results reveal a previously undescribed role for Her9/Hes4 in photoreceptor differentiation, maintenance, and survival.

developmental biology↗