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

obese mothers.

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.