The role of megalin (LRP-2/Gp330) during development.

Megalin (LRP-2/GP330), a member of the LDL receptor family, is an endocytic receptor expressed mainly in polarised epithelial cells. Identified as the pathogenic autoantigen of Heymann nephritis in rats, its functions have been studied in greatest detail in adult mammalian kidney, but there is increasing recognition of its involvement in embryonic development. The megalin homologue LRP-1 is essential for growth and development in Caenorhabditis elegans and megalin plays a role in CNS development in zebrafish.

FITC-induced murine pulmonary inflammation: CC10 up-regulation and concurrent Shh expression.

We describe an immunohistochemical study of the acute and chronic effects of fluorescein isothiocyanate (FITC) on Sonic hedgehog (Shh) expression and Clara cell secretory protein (CC10) up-regulation in murine lung. FITC was dissolved in PBS and instilled non-surgically into adult mouse lungs via the trachea. During the acute phase (120h) of the FITC response, CC10 staining within Clara cells increased markedly but the protein did not leak into the tissue spaces or the airways, and no fibrosis was apparent.

Signalling by glial cell line-derived neurotrophic factor (GDNF) requires heparan sulphate glycosaminoglycan.

Glial cell line-derived neurotrophic factor, GDNF, is vital to the development and maintenance of neural tissues; it promotes survival of sympathetic, parasympathetic and spinal motor neurons during development, protects midbrain dopaminergic neurons from apoptosis well enough to be a promising treatment for Parkinson's disease, and controls renal and testicular development. Understanding how GDNF interacts with its target cells is therefore a priority in several fields. Here we show that GDNF requires glycosaminoglycans as well as the already-known components of its receptor complex, c-Ret and GFRalpha-1.

Genes and proteins in renal development.

Metanephric kidney development begins with the formation of the metanephrogenic mesenchyme; this event depends on the prior action in the intermediate mesoderm of transcription factors such as Lim-1, Pax-2, Eya-1, and Foxc-1. Once it has formed, the mesenchyme secretes GDNF; this induces the nearby wolffian duct to produce a ureteric bud which invades the metanephrogenic mesenchyme and begins to arborize. Ureteric bud development and branching depends on the transcription factor Emx-2, the GDNF-cRet and probably the HGF/cMet, signalling systems, and the intracellular regulatory molecules formin IV and timeless.