It has been well established that changes in the environment in the uterus can affect
fetal development. It has been further shown that maternal obesity correlates with
increased risk of the development of obesity in the offspring, however the mechanism
of this relationship is not fully understood. The time period for the development of
this risk has been time-locked to the fetal period. In order to understand how a
mother’s obesity affects her offspring’s risk of obesity, we have looked to the
development of neuronal pathways in the fetal brain that are involved in weight
regulation. Disruptions to the normal development of this circuitry could be
responsible for the altered weight regulation in offspring from obese mothers.
Our lab and others have observed that the offspring of obese mothers show altered
development of axonal projections from cells in the hypothalamic arcuate nucleus
(ARC). Based on this, we hypothesised that the expression of genes that regulate axon
growth and guidance would be altered in fetuses developing in obese mothers when
compared with controls.
I have used quantitative PCR to assess gene expression in the mouse ARC at
gestational day 15.5 (GD15.5), representing mid-gestation, and early arcuate
development. Specifically, I examined the Robo and Slit gene families (Robo1,
Robo2, Robo3, Slit1 and Slit2). The results presented in this study suggest that Robo
and Slit could play a key role in the development of connections from arcuate neurons
to their targets in the hypothalamus, as we have shown that Robo and Slit genes are
present in the fetal arcuate nucleus, and have altered expression in offspring from
With the incidence of obesity in the developed and developing world reaching
epidemic proportions, an understanding of the mechanisms that underpin elevated risk
for obesity are critical in order to best confront this disease.