New clues for organogenesis.

Organogenesis is a conventional research area in developmental biology. Recent research progresses on stem cell, epigenetics, no-coding RNA and other new properties of multicellular organisms have transformed the organogenesis research as a frontier of life science. The collection of six research papers in this issue aims to cover timely developments in the research area of organogenesis from basic mechanism analysis to applied medical potential. In the first article, Dr Wu's group reported that knockdown of the members of the cadherin cell adhesion superfamily proteins, protocadherin (Pcdh) clusters, resulted in dendritic simplification and spine defects in vivo and in cultured primary hippocampal neurons in vitro. Furthermore, the knockdown of the Pcdha cluster resulted in the activation of two cell-adhesion kinases (Pyk2 and Fak) and inhibition of Rho GTPases that is essential for neuronal morphogenesis and synaptic plasticity. The authors propose that Pcdh clusters and CAKs play important roles in dendritic development and spine elaboration. In the second article, Dr Rottier's group analyzed the function of a transcription factor (TF) Sox2 in regulating the initial patterning of mouse primitive gut. The authors showed that ectopic expression of Sox2 in the posterior region of the primitive gut caused anteriorization of the gut toward a gastric-like phenotype. The authors further showed that Sox2 activated the foregut transcriptional program even in the condition of sustained co-expression of an endogenous TF Cdx2, which is recognized as a suppressor of anteriorization. They conclude that the balance between Sox2 and Cdx2 function is essential for proper specification of the primitive gut, and that Sox2 could reprogram the initial patterning of the primitive gut. It is known that a muscle-specific TF myogenin (Myog) and an MAP kinase (p38a) are required during the process of myogenesis. By comparing the expression profiling of Myog-activated alone with that of p38a activated alone in myogenesis with microarray approach, Dr Dilworth's group showed that Myog and p38a played different roles in muscle differentiation. The authors found an unexpected role for Myog in mediating cell cycle exit and identified an essential role for p38a in cell fusion through the up-regulation of CD53. It is known that genetic defects in autosomal-dominant polycystic kidney disease promote cystic growth of renal tubules, at least in part by stimulating the accumulation of cAMP. In this issue, by using bicaudal-C (Bicc1) knockout mice, Dr Constam's group reported that cAMP and its synthetic enzyme adenylate cyclase-6 were up-regulated in cystic kidneys. …