Biomedical subjects

Angelo Iulianella

Publications and source records attributed to Angelo Iulianella.

5 recordsLinked to original sources

PubMed2004

Gene expression and regulation of hindbrain and spinal cord development.

The formation of the central nervous system is one of the most fascinating processes in biology. Motor coordination, sensory perception and memory all depend on the complex cell connections that form with extraordinary precision between distinct nerve cell types within the central nervous system. The development of the central nervous system and its intricate connections occurs in several steps. During the first step known as neural induction, the neural plate forms as a uniform sheet of neuronal progenitors. Neural induction is followed by neurulation, the process in which the two halves of the neural plate are transformed into a hollow tube. Neurulation is accompanied by regionalisation of the neural tube anterior-posteriorly into the brain and spinal cord and dorso-ventrally into neural crest cells and numerous classes of sensory and motor neurons. The proper development of the vertebrate central nervous system requires the precise, finely balanced control of cell specification and proliferation, which is achieved through the complex interplay of multiple signaling systems. Bone morphogenetic proteins (BMPs), retinoic acid (RA) fibroblast growth factors (FGFs), Wnt and Hedgehog proteins are a few key factors that interact to pattern the developing central nervous system. In this review, we detail our current knowledge of the roles of these signaling factors in the development of the vertebrate nervous system in terms of the mechanisms underlying the formation and specification of the hindbrain and spinal cord.

Animals↗

PubMed2004

Immune functions in mice lacking Clnk, an SLP-76-related adaptor expressed in a subset of immune cells.

The SLP-76 family of immune cell-specific adaptors is composed of three distinct members named SLP-76, Blnk, and Clnk. They have been implicated in the signaling pathways coupled to immunoreceptors such as the antigen receptors and Fc receptors. Previous studies using gene-targeted mice and deficient cell lines showed that SLP-76 plays a central role in T-cell development and activation. Moreover, it is essential for normal mast cell and platelet activation. In contrast, Blnk is necessary for B-cell development and activation. While the precise function of Clnk is not known, it was reported that Clnk is selectively expressed in mast cells, natural killer (NK) cells, and previously activated T-cells. Moreover, ectopic expression of Clnk was shown to rescue T-cell receptor-mediated signal transduction in an SLP-76-deficient T-cell line, suggesting that, like its relatives, Clnk is involved in the positive regulation of immunoreceptor signaling. Stimulatory effects of Clnk on immunoreceptor signaling were also reported to occur in transfected B-cell and basophil leukemia cell lines. Herein, we attempted to address the physiological role of Clnk in immune cells by the generation of Clnk-deficient mice. The results of our studies demonstrated that Clnk is dispensable for normal differentiation and function of T cells, mast cells, and NK cells. Hence, unlike its relatives, Clnk is not essential for normal immune functions.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Somitogenesis: breaking new boundaries.

Segmentation is a fundamental process in vertebrate embryogenesis, and one of the earliest manifestations of segmental patterning is the generation of transient, serially repeated blocks of mesodermal cells known as somites. Disruption of the normal segmentation process in humans leads to vertebral abnormalities such as spondylocostal dysostosis. In this minireview, we discuss recent advances in the dynamic molecular and cellular mechanisms governing segmentation.

Animals↗

PubMed2003

Dynamic expression of murine Cux2 in craniofacial, limb, urogenital and neuronal primordia.

CDP/Cut homeodomain factors are a divergent group of transcriptional repressors that are conserved during metazoan evolution. The cut locus of Drosophila is required for external sensory organ development and dorso-ventral boundary formation in the wing. In vertebrates, two CDP/Cut genes have been identified, Cux1 and Cux2. While Cux1 is widely expressed in mouse embryos particularly in the nephrogenic and urogenital systems, in contrast the early embryonic expression of Cux2 has not been characterized. Here we describe the dynamic profile of Cux2 during mouse embryogenesis. Cux2 expression becomes elaborated in a number of tissues during organogenesis including the olfactory epithelium, branchial arch and limb bud progress zones, roof plate, motor neurons, dorsal root ganglia and urogenital tissues. The conservation of signaling pathways between the branchial arches and limb buds is well documented and surprisingly this can also be applied to the developing urogenital system. Cux2 expression coincides with many tissue regions undergoing proliferative growth or cell rearrangements, however some later expression domains also include sites of programmed cell death. Cux2 is hypothesized to function as a transcriptional regulator that inhibits terminal differentiation and cell cycle exit.

Animals↗

PubMed2002

Chimeric analysis of retinoic acid receptor function during cardiac looping.

Retinoids (vitamin A and its derivatives) play essential roles during vertebrate development. Vitamin A deprivation leads to severe congenital malformations affecting many tissues, including diverse neural crest cell populations and the heart. The vitamin A signal is transduced by the retinoic acid receptors (RARalpha, RARbeta, and RARgamma). However, these receptors exhibit considerable functional redundancy, as judged by the mild phenotype of RAR single null mutants relative to the defects evoked by loss of multiple RARs. To circumvent this redundancy, the endogenous RARgamma2 allele was replaced with a ligand-binding RARgamma mutant (RARgammaE(305)) by gene targeting in mouse embryonic stem (ES) cells. Chimeric embryos derived from hemizygous RARgammaE(305) ES cells displayed several defects similar to those observed in certain RAR double null mutants, including hypoplasia or absence of the caudal pharyngeal arches and myocardial deficiencies. The latter defects were not due to abnormal cardiac specification as affected hearts still expressed chamber-specific markers in an appropriate manner. Chimeras also displayed cardiac looping anomalies, which were associated with a reduction of Pitx2. This work suggests a role for RAR signaling in late looping morphogenesis and illustrates the utility of using a dominant-negative gene substitution approach to circumvent the functional redundancy inherent to the RAR family.

Animals↗