Review Epithelial biology: lessons from Caenorhabditis elegans Gre ´goire Michaux, Renaud Legouis 1 , Michel Labouesse * Institut de Ge ´ne ´tique et de Biologie Mole ´culaire et Cellulaire, CNRS /INSERM /ULP, BP. 163, F-67404 Illkirch Cedex, C.U. de Strasbourg, Strasbourg, France Received 4 May 2001; received in revised form 17 August 2001; accepted 4 September 2001 Received by A.J. van Wijnen Abstract Epithelial cells are essential and abundant in all multicellular animals where their dynamic cell shape changes orchestrate morphogenesis of the embryo and individual organs. Genetic analysis in the simple nematode Caenorhabditis elegans provides some clues to the mechan- isms that are involved in specifying epithelial cell fates and in controlling specific epithelial processes such as junction assembly, trafficking or cell fusion and cell adhesion. Here we review recent findings concerning C. elegans epithelial cells, focusing in particular on epithelial polarity, and transcriptional control. q 2001 Elsevier Science B.V. All rights reserved. Keywords: Caenorhabditis elegans; Epithelial cell; Differentiation; Morphogenesis; Adherens junction; Hemidesmosome; Extracellular matrix; Trafficking; Cell fusion; Transcription 1. Introduction Epithelial cells play an essential role during development and adult life by shaping organs, and by acting as a selective barrier to regulate the exchange of ions, growth factors or nutrients coming from the outside environment (Yeaman et al., 1999). These functions rely on proper cell fate specifica- tion and on the acquisition of a polarised phenotype. Epithe- lial cells can also easily become cancerous and a direct link between tumorigenesis, loss of cell polarity and adhesion has long been noted (Thiery et al., 1988; Behrens et al., 1989). Despite their importance and widespread occurrence, many aspects concerning the biology of epithelial cells are not fully understood. For instance, we do not know if specific transcription factors control the onset of ‘epithelialisation’ by switching on the expression of proteins that establish cell polarity. Similarly, we do not know, except in a few cases such as branching of the tracheal system (Metzger and Kras- now, 1999) and dorsal closure in Drosophila (Noselli and Agnes, 1999), which genes induce major morphogenetic processes. In addition, the detailed genetic analysis of the mechanisms underlying morphogenesis is a relatively new area, and what we know comes mainly from the fly. The nematode Caenorhabditis elegans provides another powerful system to address the questions raised above using a genetic approach in the integrated context of a live animal. Here we highlight recent progress in the analy- sis of different aspects of C. elegans epithelial biology. We first discuss specification of epithelial cell fates in the embryo (Section 3). Then we review how apico-basal polarity is established and maintained (Sections 4 and 7), how the epidermis becomes connected to the underlying muscles (Section 5), and how the basal lamina influences morphogenesis of internal epithelia (gonad, intestine and pharynx) (Sections 6, 8 and 9). Section 10 is devoted to pattern formation and morphogenesis of the egg-laying system (uterus and vulva). 2. Background anatomy There are three broad categories of epithelial cells in C. elegans: those that contribute to a classical epithelium by Gene 277 (2001) 83–100 0378-1119/01/$ - see front matter q 2001 Elsevier Science B.V. All rights reserved. PII: S0378-1119(01)00700-4 www.elsevier.com/locate/gene Abbreviations: AC, Anchor Cell; ADAM, A Disintegrin And Metallo- proteinase; AJ, Adherens Junction; CeAJ, C. elegans Apical Junction; DTC, Distal Tip Cell; DU, Dorsal Uterine (precursor); EGF, Epidermal Growth Factor; FNIII, FibroNectin type III; GFP, Green Fluorescent Protein; GPI, GlycoPhosphoInositol; GST, Glutathione S-Transferase; IF, Intermediate Filament; LC, Linker Cell; LRR, Leucine Rich Repeat; MAGUK, Membrane-Associated Guanylate Kinase; MAP, Mitogen Acti- vating Protein; MDCK, Madin–Darby Canine Kidney; PDZ, PSD95/Dlg/ ZO-1; SJ, Septate Junction; sujn, spermatheca uterine junction (uterine valve); TJ, Tight Junction; ut, uterine toroid; utse, uterine-seam (cell); uv, uterine vulva (cell); VPC, Vulval Precursor Cell; VU, Ventral Uterine (precursor) * Corresponding author. Tel.: 133-3-8865-3393; fax: 133-3-8865-3201. E-mail address: lmichel@igbmc.u-strasbg.fr (M. Labouesse). 1 Present address: CGM-CNRS, Avenue de la Terrasse, 91198 Gif/Yvette Cedex, France.