Epithelial Branching


Embryonic rudiments of most organs are composed of two types of tissues: epithelium and mesenchyme, separated by a basal lamina. Growing epithelial tissue changes and acquires a shape unique to each organ during development.

Keywords: lung; mammary gland; salivary gland; kidney; mathematical approach; branching morphogenesis; epithelial‐mesenchymal interaction

Figure 1.

A whole‐mount preparation of a mammary gland from a mouse in midpuberty. The ductal tree originates at the nipple (N) and displays many terminal end buds (large arrow) and lateral buds (small arrows). ×5.

Figure 2.

Branching morphogenesis of the developing rat lung in culture. Embryonic rat lung isolated at gestation day 13.5 (equivalent to day 11.5 gestation mouse) is shown after 1 (a), 3 (b) and 5 (c) days in culture. Extensive branching of the epithelial tubules take place in vitro. tr, trachea; pl, proximal lung; dl, distal lung. All pictures were taken under same magnification.

Figure 3.

Epithelial‐mesenchymal interactions regulate the pattern of branching of the developing lung. Diagram illustrates the basic architecture of the mouse/rat embryonic lung at the time of isolation for culture. The left lung (LL) has a single lobe, while the right lung (RL) is divided into cranial (cr), medial (m), accessory (a) and caudal (ca) lobes. Representative signalling molecules expressed in the developing lung are depicted. Epithelial Shh has its receptor patched (Ptc‐1) and other target genes in the mesenchyme. Mesenchymal FGF‐10 binds to FGFR‐2 expressed in the epithelium. The transcription factors TTF‐1 and Hox are found in the epithelium and mesenchyme, respectively.

Figure 4.

Branching morphogenesis of mouse embryonic submandibular gland. (a) A gland with a round lobule corresponding to mid 12‐day stage. (b) A gland of very late 12‐day stage with one narrow cleft (black arrow) and two small indentations (white arrows), one of which will become a definite cleft at early 13‐day stage. (c) An early 13‐day gland having three lobules separated by two narrow, deep clefts. (d) A mid to late 13‐day gland having four lobules separated by three clefts. Asterisk indicates sublingual epithelium. After Nakanishi Y and Ishii T. Epithelial shape change in mouse embryonic submandibular gland: modulation by extracellular matrix components. BioEssays11: 163–167. Copyright © 1989 by Wiley‐Liss, Inc., a subsidiary of John Wiley & Sons, Inc. All rights reserved.

Figure 5.

Simulation of lung development by a mechanical model where tissues are considered to behave as fluids of different viscosities and surface tensions. Curves represent epithelial boundary over time. Tissues in model are constrained by boundaries on two sides, but are free to expand on the third side. The physical parameters of the model are consistent with length and time scales of embryonic lung, and tissue viscosity and surface tension are estimated from in vitro experiments. After Lubkin AR and Murray JD. A mechanism for early branching in lung morphogenesis. Journal of Mathematical Biology34: 77–94. Copyright © 1995 by Springer Verlag. All rights reserved.



Bellusci S, Grindley J, Emoto H, Itoh N and Hogan BL (1997) Fibroblast growth factor 10 (FGF10) and branching morphogenesis in the embryonic mouse lung. Development 124: 4867–4878.

Bernfield M and Banerjee SD (1982) Turnover of basal lamina glycosaminoglycan correlates with epithelial morphogenesis. Developmental Biology 90: 291–305.

Cardoso WV (1995) Transcription factors and pattern formation in the developing lung. American Journal of Physiology 269: L429–L442.

Daniel CW, Robinson S and Silberstein GB (1996) The role of TGF‐beta in patterning and growth of the mammary ductal tree. Journal of Mammary Gland Biology and Neoplasia 1: 331–341.

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Hieda Y, Iwai K, Morita T and Nakanishi Y (1996) Mouse embryonic submandibular gland epithelium loses its tissue integrity during early branching morphogenesis. Developmental Dynamics 207: 395–403.

Hogan BLM (1999) Morphogenesis. Cell 96: 225–233.

Kadoya Y, Kadoya K, Durbeej M, Holmvall K, Sorokin L and Ekblom P (1995) Antibodies against domain E3 of Laminin‐1 and integrin alpha6 subunit perturb branching morphogenesis of submandibular gland, but by different modes. Journal of Cell Biology 129: 521–534.

Lubkin SR and Murray JD (1995) A mechanism for early branching in lung morphogenesis. Journal of Mathematical Biology 34: 77–94.

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Further Reading

Alt W, Deutsch A and Dunn G (eds) (1997) Dynamics of Cell and Tissue Motion. Basel: Birkhauser Verlag.

Gilbert SF (1997) Developmental Biology, 5th edn. Sunderland, MA: Sinauer Associates.

Hieda Y and Nakanishi Y (1997) Epithelial morphogenesis in mouse embryonic submandibular gland: its relationships to the tissue organization of epithelium and mesenchyme. Development, Growth and Differentiation 39: 1–8.

Humphreys RC, Lydon JP, O'Malley W and Rosen JM (1997) Use of PRKO mice to study the role of progesterone in mammary gland development. Journal of Mammary Gland Biology and Neoplasia 2: 343–354.

Lubkin SR (1997) Mechanisms for branching morphogenesis in lungs. In: Alt W, Deutsch A and Dunn G (eds) Dynamics of Cell and Tissue Motion, pp. 229–234. Basel: Birkhauser Verlag.

Neville MC and Daniel CW (1987) The Mammary Gland: Development, Regulation, and Function. New York: Plenum Press.

Saxen L (1987) Organogenesis of the Kidney. Cambridge: Cambridge University Press.

The University of Edinburgh, Anatomy Section (1998) [http://www.ana.ed.ac.uk/anatomy/database/]

Warburton D, Schwarz M, Tefft D et al. (1999) The molecular basis of lung morphogenesis. Mechanisms of Development 92: 55–81.

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Nakanishi, Yasuo, Hieda, Yohki, Cardoso, Wellington V, Lubkin, Sharon R, and Daniel, Charles W(Apr 2001) Epithelial Branching. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0001145]