BAP1 is required prenatally for differentiation and maintenance of postnatal murine enteric nervous system.

Epigenetic regulatory mechanisms are underappreciated, yet are critical for enteric nervous system (ENS) development and maintenance. We discovered that fetal loss of the epigenetic regulator Bap1 in the ENS lineage caused severe postnatal bowel dysfunction and early death in Tyrosinase-Cre Bap1fl/fl mice. Bap1-depleted ENS appeared normal in neonates; however, by P15, Bap1-deficient enteric neurons were largely absent from the small and large intestine of Tyrosinase-Cre Bap1fl/fl mice. Bowel motility became markedly abnormal with disproportionate loss of cholinergic neurons. Single-cell RNA sequencing at P5 showed that fetal Bap1 loss in Tyrosinase-Cre Bap1fl/fl mice markedly altered the composition and relative proportions of enteric neuron subtypes. In contrast, postnatal deletion of Bap1 did not cause enteric neuron loss or impaired bowel motility. These findings suggest that BAP1 is critical for postnatal enteric neuron differentiation and for early enteric neuron survival, a finding that may be relevant to the recently described human BAP1-associated neurodevelopmental disorder.

Cophylogenetic analyses of Trachymyrmex ant-fungal specificity: "One to one with some exceptions".

Over the past few decades, large-scale phylogenetic analyses of fungus-gardening ants and their symbiotic fungi have depicted strong concordance among major clades of ants and their symbiotic fungi, yet within clades, fungus sharing is widespread among unrelated ant lineages. Sharing has been explained using a diffuse coevolution model within major clades. Understanding horizontal exchange within clades has been limited by conventional genetic markers that lack both interspecific and geographic variation. To examine whether reports of horizontal exchange were indeed due to symbiont sharing or the result of employing relatively uninformative molecular markers, samples of Trachymyrmex arizonensis and Trachymyrmex pomonae and their fungi were collected from native populations in Arizona and genotyped using conventional marker genes and genome-wide single nucleotide polymorphisms (SNPs). Conventional markers of the fungal symbionts generally exhibited cophylogenetic patterns that were consistent with some symbiont sharing, but most fungal clades had low support. SNP analysis, in contrast, indicated that each ant species exhibited fidelity to its own fungal subclade with only one instance of a colony growing a fungus that was otherwise associated with a different ant species. This evidence supports a pattern of codivergence between Trachymyrmex species and their fungi, and thus a diffuse coevolutionary model may not accurately predict symbiont exchange. These results suggest that fungal sharing across host species in these symbioses may be less extensive than previously thought.