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as an invagination of the conjunctival epithelium to mesenchymal sac at the tempo-
ral region of the eye and then starts to proliferate rapidly and branch to form a lobu-
lar structure as the lacrimal gland germ (Fig. 8.1a, b) (Kammandel et  al. 1999 ;
Johnston et al. 1979 ). The fundamental structure of the lacrimal gland is achieved
by ED 19. The lacrimal gland matures by the time the eyes open 1 week after birth
and prepares to secrete tear to the ocular surface (Schechter et  al. 2010 ; Franklin
1989 ). The harderian glands in mice, which secrete tear lipids to the ocular surface,
originate from the nasal region of the conjunctival epithelium at ED 16 by similar
course of branching as the lacrimal glands and are located behind the eye (Fig. 8.1b)
(Payne 1994 ). In human, meibomian glands secrete lipids, whereas the harderian
glands are absent or rudimentary (Kozak et al. 2007 ).
The development and differentiation of the lacrimal glands are regulated by
many of the molecular signaling pathways underlying branching morphogenesis
(Fig. 8.2) (Hogan 1999 ). Pax6 expression is necessary to speculate embryonic

a

Mouse

lacrimal

gland

Day 0 Day 1 Day 2 Day 3 Day 4

In vitro culture

Mouse

harderian

gland

ED16.5 ED17.5 ED19

Thickening of

epithelium

Condense of

Mesenchyme

Initial bud Branching morphogenesis Mature gland

Acini and

myoepithelium

ED13.5

Lacrimal gland

germ

Excretory Duct

Nerve and blood

vessels

Cleft formation

b

Fig. 8.1 Embryonic organogenesis of the lacrimal glands through epithelial-mesenchymal inter-
actions. (a) Schematic representation of the lacrimal gland development. (b) Phase-contrast images
of development of the lacrimal gland germ and harderian gland germ in vitro. Scale bars, 100 μm
(Modified and reprinted from Hirayama et al^112 )

M. Hirayama et al.