A survey of hypothalamic phenotypes identifies molecular and behavioral consequences of MYT1L haploinsufficiency in male and female mice.

Dougherty, J. D.; Maloney, S. E.; McCullough, K. B.; Chaturvedi, S. M.; Selmanovic, D.; Chase, R.; Chen, J.; Wu, D.; Granadillo, J. L.; Kroll, K. L.

doi:10.1101/2024.11.25.625294

bioRxiv · 10.1101/2024.11.25.625294

A survey of hypothalamic phenotypes identifies molecular and behavioral consequences of MYT1L haploinsufficiency in male and female mice.

Dougherty, J. D.·Maloney, S. E.·McCullough, K. B.·Chaturvedi, S. M.·Selmanovic, D.·Chase, R.·Chen, J.·Wu, D.·Granadillo, J. L.·Kroll, K. L.

View original source ↗Export metadata ↓

Abstract

The transcription factor MYT1L supports proper neuronal differentiation and maturation during brain development. MYT1L haploinsufficiency results in a neurodevelopmental disorder characterized by intellectual disability, developmental delay, autism, behavioral disruptions, aggression, obesity and epilepsy. While MYT1L is expressed throughout the brain, how it supports proper neuronal function in distinct regions has not been assessed. Some features of MYT1L Neurodevelopmental Syndrome suggest disruption of hypothalamic function, such as obesity and endocrine issues, and previous research showed changes in hypothalamic neuropeptide expression following knockdown in zebrafish. Here, we leveraged our heterozygous Myt1l mutant, previously shown to recapitulate aspects of the human syndrome such as hyperactivity, social challenges, and obesity, to examine the impact of MYT1L loss on hypothalamic function. Examining the molecular profile of the MYT1L haploinsufficient hypothalamus revealed a similar scale of disruption to previously studied brain regions, yet with region-specific roles for MYT1L, including regulation of neuropeptide systems. Alterations in oxytocin and arginine vasopressin cell numbers were also found. Behaviors studied included maternal care, social group hierarchies, and aggression, all of which were unchanged. Feeding and metabolic markers were also largely unchanged in MYT1L haploinsufficient mice, yet an interaction was observed between diet and MYT1L genotype on weight gain. Our findings here suggest that gross endocrine function was not altered by MYT1L haploinsufficiency, and that key sex-specific behaviors related to proper hypothalamic function remain intact. Further study is needed to understand the functional impact of the altered hypothalamic molecular profile and changes in neuropeptide cell numbers that result from MYT1L haploinsufficiency.

Source connections

Published article ↗

Explore related subjects

animal behavior and cognition Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Dougherty, J. D., Maloney, S. E., McCullough, K. B., Chaturvedi, S. M., Selmanovic, D., Chase, R., Chen, J., Wu, D., Granadillo, J. L., Kroll, K. L.. 2024-11-25. A survey of hypothalamic phenotypes identifies molecular and behavioral consequences of MYT1L haploinsufficiency in male and female mice.. https://doi.org/10.1101/2024.11.25.625294

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Deconstructing Boldness: Latent behavioural structure across novelty, predation, and exploration in an endangered species translocation program

Risk-related behaviours including neophobia, exploration, and predator avoidance are often assumed to covary along a general boldness axis. Although some translocation studies have linked one or more of these behaviours with fitness, it is possible that the underlying behavioural structure varies under different selective environments. Conservation breeding programs provide a unique opportunity to evaluate the structure of behavioural correlations in a non-domestic species under artificial conditions. We tested whether risk-related behaviours represent a unified boldness syndrome in a captive population of the endangered Attwaters prairie chicken (APC; Tympanuchus cupido attwateri). We quantified the repeatable behaviours of 257 juveniles and compared 11 models of behavioural covariation structure using multivariate mixed models and confirmatory factor analysis. There was no support for a single risk-taking axis; instead, we found three dimensions representing responses to novelty and environmental stimuli (Engagement), predator avoidance (Threat Response), and maze exploration (Maze Progression). Our results indicate that these risk-related behaviours are not organized along a single axis in captive APCs, challenging assumptions that risk-taking represents a universal behavioural syndrome. To anticipate post-release success accurately, conservation managers should understand the exact behavioural architecture of the captive population rather than assume that the classical bold-shy structure occurs in all contexts.

animal behavior and cognition↗

bioRxiv2026

Social costs of group life: Larger groups have less affiliative behavior and more social conflict

The costs and benefits of sociality depend in part upon the size of groups. Therefore, individual behavior should vary across groups of different sizes, reflecting group size-dependent costs and benefits. Here, we test this prediction using a long-term dataset on wild female baboons (Papio cynocephalus x P. anubis). We find that individuals who live in larger groups suffer social costs: compared to animals in smaller groups, they experience more agonistic interactions, fewer grooming interactions, and sparser social networks. These social costs arise, in part, from a pattern in which relationships within dyads become more agonistic as group size increases (i.e., a given dyad exhibits fewer grooming interactions relative to agonistic interactions when it is living in a larger group). While individuals in large groups generally maintain the same number of strong bonds as individuals in small groups, they tend to develop weak bonds with a greater number of social partners that results in, on average, weaker bonds overall. Our results demonstrate that, despite potential benefits to large groups in terms of predation risk and intergroup competition, the social lives of individuals in larger groups involve less affiliation and more conflict in this wild primate population.

animal behavior and cognition↗

bioRxiv2026

Shared brain transcriptome signatures of social evolution and plasticity in shell-dwelling cichlid fishes

Inter-individual variability in phenotypic traits is widespread in nature both across and within species, with similar patterns of variation often occurring between and within species. Given that these two types of variation are generated by evolutionary and plasticity processes respectively, it raises the question to what extent the causal mechanisms underlying such variability at these two different levels are shared or not. To address this question, we studied the variation in brain transcriptomes in Tanganyikan cichlids that exhibit both intra- and interspecific variation in social behavior. We compared two facultatively social cichlid species, each containing naturally occurring solitary and social-living individuals, with a closely related obligatory solitary resembling the ancestral state. Differential gene expression and Gene Set Enrichment Analyses were performed in the telencephalon and diencephalon transcriptomes to investigate the molecular basis of both behavioral plasticity and the evolution of sociality. Behavioral plasticity involved few differentially expressed genes but extensive changes in biological pathways, supporting a highly polygenic architecture of social behavior. Across both species, social-living individuals consistently upregulated pathways involved in translation, protein homeostasis, and energy metabolism, whereas solitary individuals showed enrichment of neuronal morphogenesis, cell adhesion, and structural plasticity. Remarkably, these same functional programs were associated with the independent evolution of sociality, revealing a strong overlap between evolutionary and plastic transcriptional responses. This convergence was largely restricted to the telencephalon, while the diencephalon showed limited and inconsistent functional signatures. Together, our results support the repeated recruitment of gene regulatory programs during the evolution of sociality and demonstrate that behavioral plasticity and evolutionary transitions share common neurogenomic responses, consistent with a conserved genetic toolkit for social behavior.

animal behavior and cognition↗