Isthmin-1: A critical regulator of branching morphogenesis and metanephric mesenchyme condensation during early kidney development.

Isthmin-1 (Ism1) was first described to be syn-expressed with Fgf8 in Xenopus. However, its biological role has not been elucidated until recent years. Despite of accumulated evidence that Ism1 participates in angiogenesis, tumor invasion, macrophage apoptosis, and glucose metabolism, the cognate receptors for Ism1 remain largely unknown. Ism1 deficiency in mice results in renal agenesis (RA) with a transient loss of Gdnf transcription and impaired mesenchyme condensation at E11.5. Ism1 binds to and activates Integrin α8ß1 to positively regulate Gdnf/Ret signaling, thus promoting mesenchyme condensation and ureteric epithelium branching morphogenesis. Here, we propose the hypothesis underlying the mechanism by which Ism1 regulates branching morphogenesis during early kidney development.

Holmgren's principle of delamination during fin skeletogenesis.

During fin morphogenesis, several mesenchyme condensations occur to give rise to the dermal skeleton. Although each of them seems to create distinctive and unique structures, they all follow the premises of the same morphogenetic principle. Holmgren's principle of delamination was first proposed to describe the morphogenesis of skeletal elements of the cranium, but Jarvik extended it to the development of the fin exoskeleton. Since then, some cellular or molecular explanations, such as the "flypaper" model (Thorogood et al.), or the evolutionary description by Moss, have tried to clarify this topic. In this article, we review new data from zebrafish studies to meet these criteria described by Holmgren and other authors. The variety of cell lineages involved in these skeletogenic condensations sheds light on an open discussion of the contributions of mesoderm- versus neural crest-derived cell lineages to the development of the head and trunk skeleton. Moreover, we discuss emerging molecular studies that are disclosing conserved regulatory mechanisms for dermal skeletogenesis and similarities during fin development and regeneration, which may have important implications in the potential use of the zebrafish fin as a model for regenerative medicine.