Hormonal gatekeeping via the blood brain barrier governs behavior

Abstract

Here we reveal an unanticipated role of the blood-brain-barrier (BBB) in regulating complex social behavior in ants. Using scRNA-seq we find localization in the BBB of a key hormone-degrading enzyme called Juvenile hormone esterase (Jhe), and we show that this localization governs the level of Juvenile Hormone (JH3) entering the brain. Manipulation of the Jhe level reprograms the brain transcriptome between ant castes. While ant Jhe is retained and functions intracellularly within the BBB, we show that Drosophila Jhe is naturally extracellular. Heterologous expression of ant Jhe into the Drosophila BBB alters behavior in fly to mimic what is seen in ant. Most strikingly, manipulation of Jhe levels in ant reprograms complex behavior between worker castes. Our study thus uncovers a novel, potentially conserved role of the BBB serving as a molecular gatekeeper for a neurohormonal pathway that regulates social behavior.

From egg to adult: a developmental table of the antMonomorium pharaonis

“…To date, empirical eco-evo-devo studies on ants have helped us to understand queen-worker caste differentiation (Wheeler 1986, Abouheif and Wray 2002, Sameshima et al 2004, Gotoh et al 2005, Khila and Abouheif 2008, Khila and Abouheif 2010, Miyazaki et al 2010, Penick et al 2012, Qui et al 2018, Chandra et al 2018, Nagel et al 2020, Qui et al 2022, Yan et al 2022, Trible et al 2023, epigenetic regulation (Alvarado et al 2015, LeBoeuf et al 2016, Simola et al 2016, Glastad et al 2021, Gospocic et al 2021, worker polymorphism (Wheeler and Nijhout 1981a, Wheeler and Nijhout 1981b, Klein et al 2018 , social behaviour (Teseo et al 2014, Trible et al 2017, Yan et al 2017, Glastad et al 2021, Gospocic et al 2021, Brahma et al 2023, Ju et al 2023, modularity (Yang and Abouheif 2011, Londe et al 2015, Hart et al 2024, evolutionary novelty (Rajakumar et al 2012, Favé et al 2015, Powell et al 2020, Rafiqi et al 2020, gene by environment interactions (Schrader et al 2014, Singh and Linksvayer 2020, Schrader et al 2021, ...…”

“…For example, the ability to establish transgenic lines with CRISPR-CAS9 gene editing in any organism is predicated on a working knowledge of the timing and stages of that organism's development. This is evident in recent studies that have functionally manipulated gene expression during development in different ant lineages, where an understanding of developmental timing was required to ensure the specificity and efficacy of reagents to downregulate gene expression (Alvarado et al 2015, Trible et al 2017, Yan et al 2017, Rafiqi et al 2020, Gospocic et al 2021, Qui et al 2022Yan et al 2022, Ju et al 2023, Hart et al 2023.…”

Social administration of juvenile hormone to larvae increases body size and nutritional needs for pupation

“…Assessing the economical aspect of this division of labour requires measuring the physiological costs of synthesis of juvenile hormone as well as benefits of receiving it socially. Furthermore, it has been recently shown that C. floridanus have evolved a form of juvenile hormone esterase in the blood brain barrier [52] that protects individual's brains from juvenile hormone which might otherwise affect their behaviour. Potentially this enzyme might represent an adaptation to ensure worker behavioural integrity, despite the high titre of juvenile hormone that must be produced to be fed to larvae.…”

Social administration of juvenile hormone to larvae increases body size and nutritional needs for pupation

“…Assessing the economical aspect of this division of labour requires measuring the physiological costs of synthesis of juvenile hormone as well as benefits of receiving it socially. Furthermore, it has been recently shown that C. floridanus have evolved a form of juvenile hormone esterase in the blood brain barrier [52] that protects individual's brains from juvenile hormone which might otherwise affect their behaviour. Potentially this enzyme might represent an adaptation to ensure worker behavioural integrity, despite the high titre of juvenile hormone that must circulate to be fed to larvae.…”