Loading...
3 results
Search Results
Now showing 1 - 3 of 3
- Numb/Numbl-Opo antagonism controls retinal epithelium morphogenesis by regulating integrin endocytosisPublication . Bogdanović, Ozren; Delfino-Machín, Mariana; Nicolás-Pérez, María; Gavilán, María P.; I, Gago-Rodrigues; Fernández-Miñán, Ana; Lillo, Concepción; Ríos, Rosa M.; Wittbrodt, Joachim; Martínez-Morales, Juan R.Polarized trafficking of adhesion receptors plays a pivotal role in controlling cellular behavior during morphogenesis. Particularly, clathrin-dependent endocytosis of integrins has long been acknowledged as essential for cell migration. However, little is known about the contribution of integrin trafficking to epithelial tissue morphogenesis. Here we show how the transmembrane protein Opo, previously described for its essential role during optic cup folding, plays a fundamental role in this process. Through interaction with the PTB domain of the clathrin adaptors Numb and Numbl via an integrin-like NPxF motif, Opo antagonizes Numb/Numbl function and acts as a negative regulator of integrin endocytosis in vivo. Accordingly, numb/numbl gain-of-function experiments in teleost embryos mimic the retinal malformations observed in opo mutants. We propose that developmental regulator Opo enables polarized integrin localization by modulating Numb/Numbl, thus directing the basal constriction that shapes the vertebrate retina epithelium.
- Usage of medical cannabis in elderly patients with chronic pain associated diseasesPublication . I, Gago-Rodrigues; Pais, Sandra; Nascimento, João; Águas, FernandoThe use of cannabis plant for medical proposes is a millenary practice, there were found evidences of its usage in India by 1000 BC. The pharmacological benefits and proprieties of cannabis are explore since ancient era, however its consumption was criminalized in various countries, starting in the beginning for 19th century until nowadays
- Analysis of opo cis-regulatory landscape uncovers Vsx2 requirement in early eye morphogenesisPublication . I, Gago-Rodrigues; Fernández-Miñán, Ana; Letelier, Joaquin; Naranjo, Silvia; Tena, Juan J.; Gómez-Skarmeta, José L.; Martinez-Morales, Juan R.The self-organized morphogenesis of the vertebrate optic cup entails coupling the activation of the retinal gene regulatory network to the constriction-driven infolding of the retinal epithelium. Yet the genetic mechanisms underlying this coordination remain largely unexplored. Through phylogenetic footprinting and transgenesis in zebrafish, here we examine the cis-regulatory landscape of opo, an endocytosis regulator essential for eye morphogenesis. Among the different conserved enhancers identified, we isolate a single retina-specific element (H6_10137) and show that its activity depends on binding sites for the retinal determinant Vsx2. Gain- and loss-of-function experiments and ChIP analyses reveal that Vsx2 regulates opo expression through direct binding to this retinal enhancer. Furthermore, we show that vsx2 knockdown impairs the primary optic cup folding. These data support a model by which vsx2, operating through the effector gene opo, acts as a central transcriptional node that coordinates neural retina patterning and optic cup invagination in zebrafish.