Maternal photoperiodic programming


Life on a rotating planet brings predictable daily and seasonal environmental challenges to the balancing of energy budgets for biological fitness. Because thermo-energetic challenges are inversely related to body size, the capacity to predict the cyclical environmental changes is of special importance for small animals, and above all in the neonatal / juvenile period. The light-dark cycle and annually changing day lengths (photoperiod), are the most predictable information sources regarding the time of the day and time of the year. Adult mammals are in direct contact with the photic environment, and translate this signal via the hormone melatonin, to time their own changes in physiology and behaviour. Contrastingly, the foetus is isolated from photoperiodic information both because light levels in utero are much lower than in the surrounding environment, and light sensing pathways are not fully developed until after birth in many cases. To deal with this challenge, mammals use maternal melatonin as a transplacental signal, through which the foetus gains information about time of day, and about time of year. We call this phenonmenon maternal photoperiodic programming (MPP).

This research area is under investigation from an eco-evolutionary approach and a mechanistic approach.  

Research into MPP under theme 1 focuses on the mechanisms, through which birth date sets the life-history trajectory of small mammals. Maternal photoperiodic programming (MPP) is a major seasonal adaptive strategy for arctic rodent species, and presents an excellent paradigm for studying developmental programming mechanisms controlling metabolic and reproductive physiology. MPP depends on day length exposure in pregnancy being transmitted to the fetus via maternal production of melatonin, and sets pups on fast or slow maturation trajectories, according to time of year of birth. The maternal melatonin signal is both necessary and sufficient for this programming, and acts through well-defined receptor signalling pathways, making this a highly tractable experimental model. 

This project will identify cells that are the targets of MPP during development, how this influences their fate, and how epigenetic mechanisms are involved in this process. These studies will be extended to consider how programming couples to hypothalamic function, specifically energy metabolism in early life, which is of crucial importance for mammals and birds in arctic environments because efficient regulation of energy metabolism is required for survival. Importantly this research also has relevance to human hypothalamic and endocrine dysfunction. 

Under theme 2 MPP is an excellent paradigm to investigate novel genetic loci linked to seasonal adaptation, which we can follow-up in comparative laboratory experiments.  Vole species are particularly useful in this regard due to their wide latitudinal range and tractability as a laboratory species. We recently de novo assembled genomes for two species of vole, Microtus arvalis and M. oeconomus and are using these in whole genome resequencing and Fst analysis of variant populations from the northern and southern areas. This approach has successfully isolated a number of novel loci linked to seasonal adaptation, which we can follow-up in comparative laboratory experiments in the two species.These comparative analyses are unbiased in their genetic focus, and provide a powerful complementary tool to the focussed approaches under Theme 1.

Under theme 3 MPP is a powerful paradigm in which prenatal experience sets seasonal timer function through to adulthood and is influenced by the environment. We see this plasticity in timing as an epigenetic phenomenon in which the expression of outputs of the core timer, or possibly even the timer itself is modulated by environmental factors. As we have established a  MPP paradigm in rodents (hamsters, MSM mice and voles) we will continue this work by dissecting how this epigenetic influence is exerted at gene expression and brain metabolism levels, and extend the experimental paradigm to explore species variation in photoperiod x temperature and photoperiod x food interactions. 



Members:

David Grey Hazlerigg (Principal investigator)
Vebjørn Jacobsen Melum
Shona Wood


Financial/grant information:

Tromsø forskningsstiftelse (TFS) starter grant TFS2016SW, fonds Paul-Mandel pour les neurosciences, and the Norwegian research council Aurora travel grant, awarded to Shona Wood. HFSP program grant
RGP0030/2015-C301 "Evolution of seasonal timers", awarded to David Hazlerigg.