Abstract Laminin-5 is known to be an integral part of the hemidesmosome and therefore responsible for the in- tegrity of the connection of the epithelium to the base- ment membrane. This is also an important mechanism during embryonic development, as documented by stud- ies in mice. In an attempt to elucidate its implication for human development we localised the mRNA of the α3 chain of laminin with the help of in situ RT-PCR, and the laminin-5 protein immunohistochemically. We systemat- ically investigated kidney, lung, skin and intestinal tissue of consecutive developmental stages during human em- bryogenesis. From gw 6.5 onwards, the mRNA of the α3 chain of laminin was found exclusively in the cytoplasm of epithelial cells of the developing kidney, lung, skin and intestine. Interestingly, in the skin and intestine from gw 8 onwards, the superficial cell layers also stained positive for the mRNA, while the protein was still only found in the dermal-epidermal and enteric basement membrane zones. In all developing organs investigated, the mRNA of the α3 chain of laminin is strictly of epi- thelial origin and the corresponding protein localised in the underlying basement membrane zones. Due to this discrepancy, we postulate a broader role for laminin-5 during human embryogenesis, for example, for epithelial cell development, beyond its involvement in hemides- mosome formation and cell adhesion. Keywords Human lung · Skin · Intestine · Kidney development · Laminin-5 Introduction Laminins are the major basement membrane components of most tissues (Timpl 1996) and appear already at the very early stages of mouse development (Cooper and MacQueen 1983). Laminin-1 is the first basement mem- brane component present during early basement mem- brane formation in the day 7 mouse embryo (Miosge et al. 1993, 2000b). Laminins regulate multiple cell biolog- ical functions, from cell growth and differentiation, mi- gration and adhesion to tissue regeneration and wound healing (Timpl 1996). Among the fourteen laminin iso- forms so far known (Koch et al. 1999; Libby et al. 2000), laminin-5 might be viewed as the cutaneous basement membrane zone laminin, and amongst others, is one of the major components of the hemidesmosome (Rousselle et al. 1991). The α2 chain of laminin-2/-4 is known to be mutated in muscular dystrophy, and all three chains of laminin-5 are involved in the development of heritable blistering diseases (Ryan et al. 1996), the very severe form of lethal junctional epidermolysis bullosa type Her- litz being one of them (Aberdam et al. 1994a; Christiano and Uitto 1996). Laminin-5 is composed of three chains, the α3, β3 and γ2 chains (Rousselle et al. 1991; Burgeson et al. 1994) and exhibits the typical cross-shaped appearance of all laminins (Timpl 1996). The γ2 chain has a very low binding affinity for nidogen, and laminin-5 is inte- grated into basement membrane via laminin-6/-7 (Champliaud et al. 1996). Two transcripts of the γ2 chain have been described in mice (Airenne et al. 2000). For the α3 chain, two transcriptional splice variants, the α3a and α3b chains, are known for humans (Ryan et al. 1994; Vidal et al. 1995). The α3a chain is proteolytically processed twice from 200 kD to 165 kD to 145 kD by cleavage of the c-terminal G-domain and the n-terminal N. Miosge ( ✉ ) · J.-G.A. Kluge · A. Studzinski · C. Zelent P. Sprysch · R. Herken Department of Histology, University of Göttingen, Kreuzbergring 36, 37075 Göttingen, Germany e-mail: nmiosge@gwdg.de Tel.: +49-551-3912925, Fax: +49-551-397067 C. Bode Department of Molecular Biology, University of Göttingen, Kreuzbergring 36, 37075 Göttingen, Germany R.E. Burgeson Cutaneous Biology Research Center, Department of Dermatology, Harvard Medical School, Charlestown, Boston, MA, USA Anat Embryol (2002) 205:355–363 DOI 10.1007/s00429-002-0256-7 ORIGINAL ARTICLE Nicolai Miosge · Jens-Gerrit Alexander Kluge Arthur Studzinski · Christina Zelent · Christa Bode Patricia Sprysch · Robert E. Burgeson · Rainer Herken In situ-RT-PCR and immunohistochemistry for the localisation of the mRNA of the alpha 3 chain of laminin and laminin-5 during human organogenesis Accepted: 21 March 2002 / Published online: 28 June 2002 © Springer-Verlag 2002