Biomedical subjects

Josana Rodríguez

Publications and source records attributed to Josana Rodríguez.

4 recordsLinked to original sources

PubMed2004

Morphogens as growth cone signalling molecules.

Morphogen signalling among cells is one of the most important mechanisms underlying the progressive patterning of embryos. Members of the hedgehog (Hh), wingless (Wnt), transforming growth factor-beta (TGFbeta), and fibroblast growth factor (Fgf) families of extracellular signalling molecules act as morphogens. Recent studies have demonstrated that members of these four families of proteins, secreted by well-characterised organiser centres in the central nervous system (CNS) as floor plate or midbrain-hindbrain boundary, are reused at later developmental stages to control axon growth. Here, we have summarised the evidence for this novel idea with a particular emphasis on those related to Shh and Wnt signalling-the object of some works in our laboratory.

Animals↗

PubMed2004

Evaluation of SFRP1 as a candidate for human retinal dystrophies.

PURPOSE: Secreted Frizzled Related Proteins (SFRPs) are soluble molecules capable of modulating Wnt signalling. Different lines of evidence indicate that SFRP activity is related with the development and function of the retina photoreceptor cells as well as with their apoptotic degeneration associated with the onset of different cases of retinal dystrophy (RD). Because the genetic causes of many retinal dystrophies still need to be determined, we have asked whether mutations in the SFRP genes might be associated with retinal dystrophies. METHODS: Here we describe the genomic structure of SFRP1, SFRP2, and SFRP5 and a mutational screening of SFRP1 in 325 individuals affected by various non X-linked forms of inherited retinal disorders. RESULTS: Three polymorphic variants were identified. CONCLUSIONS: Our data, so far, exclude SFRP1 as a molecular cause of RD, since two out of three genetic variants of the gene were present in both RD patients and normal population.

Adaptor Proteins, Signal Transducing↗

PubMed2003

SFRP1 modulates retina cell differentiation through a beta-catenin-independent mechanism.

Secreted frizzled related proteins (SFRPs) are soluble molecules capable of binding WNTS and preventing the activation of their canonical signalling cascade. Here we show that Sfrp1 contributes to chick retina differentiation with a mechanism that does not involve modifications in the transcriptional activity of beta-catenin. Thus, addition of SFRP1 to dissociated retinal cultures or retroviral mediated overexpression of the molecule consistently promoted retinal ganglion and cone photoreceptor cell generation, while decreasing the number of amacrine cells. Measure of the activity of the beta-catenin-responsive Tcf-binding site coupled to a luciferase reporter in transiently transfected retinal cells showed that Sfrp1 was unable to modify the basal beta-catenin transcriptional activity of the retina cells. Interestingly, a dominant-negative form of GSK3beta gave similar results to those of Sfrp1, and a phosphorylation-dependent inhibition of GSK3beta activity followed SFRP1 treatment of retina cells. Furthermore, retroviral mediated expression of a dominant-negative form of GSK3beta induced a retina phenotype similar to that observed after Sfrp1 overexpression, suggesting a possible involvement of this kinase in SFRP1 function.

Amacrine Cells↗

PubMed2002

DNA polymerase lambda, a novel DNA repair enzyme in human cells.

DNA polymerase lambda (pol lambda) is a novel family X DNA polymerase that has been suggested to play a role in meiotic recombination and DNA repair. The recent demonstration of an intrinsic 5'-deoxyribose-5-phosphate lyase activity in pol lambda supports a function of this enzyme in base excision repair. However, the biochemical properties of the polymerization activity of this enzyme are still largely unknown. We have cloned and purified human pol lambda to homogeneity in a soluble and active form, and we present here a biochemical description of its polymerization features. In support of a role in DNA repair, pol lambda inserts nucleotides in a DNA template-dependent manner and is processive in small gaps containing a 5'-phosphate group. These properties, together with its nucleotide insertion fidelity parameters and lack of proofreading activity, indicate that pol lambda is a novel beta-like DNA polymerase. However, the high affinity of pol lambda for dNTPs (37-fold over pol beta) is consistent with its possible involvement in DNA transactions occurring under low cellular levels of dNTPs. This suggests that, despite their similarities, pol beta and pol lambda have nonredundant in vivo functions.

Amino Acid Sequence↗