Elucidating the role of macrophages during salivary gland development

The correct growth, morphogenesis and patterning of an organ or tissue during development is essential for its function in adulthood. The majority of organs (such as heart, lungs, intestine), develop during the embryonic period in order to be functional by birth, while others (e.g. lymphoid structures and the salivary glands) continue to mature into the neonatal period or into puberty (such as the mammary glands). The salivary glands (SG) develop through a process known as branching morphogenesis, where the glandular epithelium undergoes rounds of branching and clefting, to create a branched organ which is capable, by the time of weaning, of saliva production. A number of precisely timed signalling events are necessary for this correct growth and patterning, and the phenomenon involves multiple cells working together.
Recent studies have implicated macrophages (Mf) as having a pivotal role in organ development, in addition to their classical phagocytic roles. Mouse mammary gland Mf are recruited to the epithelium and provide vital cues for branching morphogenesis during embryogenesis. Furthermore, Mf-deficient mice experience altered mammary gland branching and elongation during puberty and pregnancy, resulting in a lactational defect. Similarly, Mf are recruited to the developing pancreas and kidney, and their absence results in abnormal development. While we have recently explored the role of Mf in SG regeneration, and we have shown that Mf are necessary for efficient epithelial regeneration after injury in adulthood, it is not known whether Mf play a key role in SG development. In preliminary data we have shown, for the first time, that a mouse model which exhibits macrophage deficiency (the Csf1rFIRE/FIRE mouse) displays aberrant SG development.
Thus, in this project we will ascertain how macrophages influence salivary gland development and branching morphogenesis.
We will address this question via 3 aims:
Aim 1: Characterise how SG development occurs in the...