Biology subjects

Jackson, D. G.

Publications and source records attributed to Jackson, D. G..

3 recordsLinked to original sources

bioRxiv2026

Distinct roles of the Lyve1 lineage in heart development

Lyve1Cre is widely used to study lymphatic endothelial cells, but its activity in the embryonic heart has not been comprehensively defined. Here we show that the Lyve1 lineage contributes to multiple cardiovascular cell types, including venous endothelium of the sinus venosus forming coronary vessels, endocardial cells generating complementary coronary territories and valve structures, lymphatic endothelial cells required for cardiac lymphatic development, and tissue-resident macrophages within the embryonic myocardium. Functional perturbations demonstrated that Notch1 gain-of-function in Lyve1+ lineages disrupted vascular development, while Prox1 deletion caused severe edema, blood-filled lymphatics, and perinatal lethality. Mid-gestation mutants exhibited underdeveloped, blood-filled lymphatics despite intact blood vasculature, and by late gestation cardiac lymphatics were depleted. These findings reveal distinct cardiovascular roles of the Lyve1 lineage and establish Lyve1Cre as a versatile but non-specific tool, underscoring the need for careful interpretation when investigating heart development and regenerative processes.

developmental biology↗

bioRxiv2025

Lymphatic dissemination drives systemic invasion by diverse clinically relevant extracellular bacterial pathogens

Extracellular bacterial pathogens cause an estimated 6 million deaths annually and drive antimicrobial resistance. Systemic bacterial infection is typically attributed to direct blood vessel invasion or intracellular transit, while draining lymph nodes are generally assumed to trap and eliminate extracellular bacteria to prevent onward lymphatic spread. However, we previously demonstrated that Streptococcus pyogenes disseminates extracellularly via the lymphatic system. Here, we show that lymphatic dissemination extends across diverse clinically important extracellular bacterial pathogens, including Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus agalactiae. In a murine soft tissue infection model, clinical isolates reached local draining lymph nodes, sequential distant draining lymph nodes, and systemic organs. In contrast,non-draining lymph nodes contained few or no bacteria, even during bacteraemia, consistent with lymphatic spread rather than haematogenous seeding. Dissemination efficiency varied between species and among isolates, with S. aureus largely restricted to local draining lymph nodes. Notably, capsular polysaccharide enhanced lymphatic dissemination independently of bacterial burden at the infection site. These findings identify lymphatic dissemination as a common route of invasion by extracellular bacterial pathogens, exposing sequential draining lymph nodes to viable bacteria.

immunology↗

bioRxiv2020

Tissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart

Macrophages are components of the innate immune system with key roles in tissue inflammation and repair. It is now evident that macrophages also support organogenesis, but few studies have characterized their identity, ontogeny and function during heart development. Here, we show that resident macrophages in the subepicardial compartment of the developing heart coincide with the emergence of new lymphatics and interact closely with the nascent lymphatic capillaries. Consequently, global macrophage-deficiency led to extensive vessel disruption with mutant hearts exhibiting shortened and mis-patterned lymphatics. The origin of cardiac macrophages was linked to the yolk sac and fetal liver. Moreover, Csf1r+ and Cx3cr1+ myeloid sub-lineages were found to play essential functions in the remodeling of the lymphatic endothelium. Mechanistically, macrophage hyaluronan was found to be required for lymphatic sprouting by mediating direct macrophage-lymphatic endothelial cell interactions. Together, these findings reveal insight into the role of macrophages as indispensable mediators of lymphatic growth during the development of the mammalian cardiac vasculature.Summary statement Tissue-resident macrophages are indispensable mediators of lymphatic vessel formation during heart development and function to remodel the vascular plexus.View Full Text

developmental biology↗