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Rodriguez, I.

Publications and source records attributed to Rodriguez, I..

2 recordsLinked to original sources

Spatio-temporal regulation of Dachsous proteins expressed during Drosophila development

Transcriptional regulation is one of the main mechanisms involved in tissue morphogenesis to give rise to functional organs with characteristic shapes. The Drosophila dachsous (ds) gene plays a key role in tissue development and tumorigenesis by controlling planar cell polarity (PCP), tissue growth, patterning and mitochondrial activity, among other processes. Disturbance of ds expression during Drosophila development results in alterations of the function and morphology of a wide range of embryonic and larval tissues. Similarly, in humans, mutations in the DCHS1 gene cause severe congenital malformations due to a global impairment affecting the normal formation of many tissues and organs. However, the transcriptional mechanism governing the expression of ds gene remains poorly understood. Here, we perform transcriptional analysis of ds expression and identify novel embryonic Ds proteins not expressed in larvae. The comparative analysis of Ds proteins and the exon expression pattern in/of two regulatory alleles such as dsD36 and ds38K further suggests the existence of specific transcriptional ds variants at different stages. Furthermore, a search for regulatory elements that control the spatial and temporal pattern of ds revealed the presence of cis-regulatory elements located in the intronic regions, which regulate the expression of these Ds proteins. Finally, using the Drosophila wing as model to perform a functional analysis, we show that wing growth and PCP are differentially regulated by Ds proteins expressed in different regions of wing disc. The present findings reveal that the complex regulation of the ds gene ensures the expression of specific Ds protein isoforms at different developmental stages in order to activate the cell-specific molecular programs required for tissue morphogenesis.

genetics

Restoring wild type-like network dynamics and behaviour during adulthood in a mouse model of schizophrenia

Schizophrenia is a severely debilitating neurodevelopmental disorder. Establishing a causal link between circuit dysfunction and particular behavioural traits relevant to schizophrenia is crucial to shed new light on the mechanisms underlying the pathology. Here we studied an animal model of the 22q11 deletion syndrome, which is the highest genetic risk to develop the pathology. We report a desynchronization of hippocampal neuronal assemblies that resulted from parvalbumin interneuron hypoexcitability. Rescuing parvalbumin interneuron excitability with pharmacological or chemogenetic approaches is sufficient to restore wild type-like network dynamics and behaviour during adulthood. In conclusion, our data provide mechanistic insights underlying network dysfunction relevant to schizophrenia and demonstrate the potential of reverse engineering in fostering new therapeutic strategies to alleviate the burden of neurodevelopmental disorders.

neuroscience