Tissue Development, Repair, and Remodeling - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 675

In mouse embryos, the submandibular salivary glands appear at mid-gestation
as small epithelial buds on the floor of the oral cavity. Buds and stalks of
the developing submandibular gland contain multipotent stem cells. Nerves that
originate from parasympathetic ganglia innervate epithelial buds to support their
development via neurotransmitter acetylcholine and acetylcholine muscarinic M 1
receptor. At least in mouse embryonic salivary glands, parasympathetic innervation
preferentially signals to keratin-5 , epithelial progenitor cell population via mus-

carinic receptor [ 1385 ]. Furthermore, cholinergic stimulation triggers the release
of heparin-binding epidermal growth factor that binds to epidermal growth factor
receptor. These progenitor cells are then maintained in the adult salivary gland.
Therefore, innervation not only controls organ function, but also contributes to organ
repair and regeneration, as it maintains a progenitor cell population.

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11.1.4 Regulation of Organogenesis

Organogenesis regulation involves various DNA-binding proteins, such as tran-
scription factors, nuclear receptors, and their coactivators and inhibitors, as well
as signaling messengers, such as growth factors and hormones, in addition to
mechanical constraints. Triggered pathways modulate cell functioning and secretion
of constituents of the extracellular matrix and its organization. Various growth
factors and hormones bind to their specific receptors and provoke protein synthesis,
and post-translational modifications of proteins, as well as exocytosis of substances.
Any morphogen influences the fate of its target cells in a dose-dependent manner to
direct regional specialization within a developing tissue or organ.
Many other regulators influence embryo- and fetogenesis, as they modulate gene
transcription for patterning factors, such as vitamin-A and its metabolites [ 1386 ].
Retinoic acid contributes to the control of cell division and differentiation in tissues
of ecto-, endo-, and mesodermal origin via cognate transcription factor, the nuclear
retinoic acid (RAR or NR1b) and retinoid-X (RXR or NR2b) receptors.
Retinoic acid, the active form of vitamin-A, has many functions during embryo-
genesis. In adults, it regulates fertility, maintains normal vision, and prevents tumor
growth and degenerative diseases. This small lipophilic molecule binds to nuclear
receptors that are heterodimers of retinoic acid receptors and retinoid X receptors
(RAR-RXR complexes; Vol. 3 - Chap. 6. Receptors) to regulate the transcriptional
activity of target genes. Retinoic acid is synthesized from inactive precursors (retinol
or β -carotene) from food after digestive processing that leads to plasmatic transport