Figure 7.

NOTCH signaling may regulate lacrimal gland branching by controlling the transition from proliferative progenitor state into postmitotic differentiation state. (A) At the earliest stages of development, Notch positive lacrimal gland progenitors (yellow) proliferate, growing radially outward like an expanding balloon. (B) Cessation of Notch signaling causes some progenitors to exit the cell cycle and become Notch negative, differentiated cells (red). (C) Unlike Notch positive proliferating progenitors, Notch negative postmitotic cells secrete ECM (blue), which accumulates between them to form physical barriers (“clefts”). Progenitors express MMPs, enzymes that degrade ECM and allow the proliferating cells to continue their radial expansion. Consequently, the glandular tissue expands outward like a balloon being inflated against a solid structure. (D) Recursive iteration of this process gives rise to the complex branching and multilobular structure that is the mature lacrimal gland.