Organogenesis of the exocrine gland.

Morphogenesis of exocrine glands is a complex stepwise process of epithelial ingrowth, ductal elongation, ductal branching, and alveolar or acinar differentiation. Emerging from an increasing number of mouse gene knockout, dominant-negative, and antisense models is the identification of a remarkable collection of cell adhesion molecules, growth factors, and their receptors whose time-dependent contributions to glandular organogenesis are essential. Many have cryptically overlapping and interdependent but noncompensatory roles. Discoidin domain receptor 1 tyrosine kinase (DDR1) and the ErbB1 receptor of amphiregulin are, for example, required for ductal branching and elongation. Each is in turn dependent on the Wnt family of morphogenic factors for autophosphorylation or transactivation, respectively. Here we review the current cast of exocrine glandular morphogens, as a foundation for a global or systems biology appreciation of the interweaving signaling pathways that underlie mammalian glandular morphogenesis.