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Neuronal morphogenesis, integration into circuits, and remodeling of synaptic connections occur in temporally and spatially defined steps. Accordingly, the expression of proteins and specific protein isoforms that contribute to these processes must be controlled quantitatively in time and space. A wide variety of post-transcriptional regulatory mechanisms, which act on pre-mRNA and mRNA molecules contribute to this control. They are thereby critically involved in physiological and pathophysiological nervous system development, function, and maintenance. Here, we review recent findings on how mRNA metabolism contributes to neuronal development, from neural stem cell maintenance to synapse specification, with a particular focus on axon growth, guidance, branching, and synapse formation. We emphasize the role of RNA-binding proteins, and highlight their emerging roles in the poorly understood molecular processes of RNA editing, alternative polyadenylation, and temporal control of splicing, while also discussing alternative splicing, RNA localization, and local translation. We illustrate with the example of the evolutionary conserved Musashi protein family how individual RNA-binding proteins are, on the one hand, acting in different processes of RNA metabolism, and, on the other hand, impacting multiple steps in neuronal development and circuit formation. Finally, we provide links to diseases that have been associated with the malfunction of RNA-binding proteins and disrupted post-transcriptional regulation.

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Synaptic targeting with subcellular specificity is essential for neural circuit assembly. Developing neurons use mechanisms to curb promiscuous synaptic connections and to direct synapse formation to defined subcellular compartments. How this selectivity is achieved molecularly remains enigmatic. Here, we discover a link between mRNA poly(A)-tailing and axon collateral branch-specific synaptic connectivity within the CNS. We reveal that the RNA-binding protein Musashi binds to the mRNA encoding the receptor protein tyrosine phosphatase Ptp69D, thereby increasing poly(A) tail length and Ptp69D protein levels. This regulation specifically promotes synaptic connectivity in one axon collateral characterized by a high degree of arborization and strong synaptogenic potential. In a different compartment of the same axon, Musashi prevents ectopic synaptogenesis, revealing antagonistic, compartment-specific functions. Moreover, Musashi-dependent Ptp69D regulation controls synaptic connectivity in the olfactory circuit. Thus, Musashi differentially shapes synaptic connectivity at the level of individual subcellular compartments and within different developmental and neuron type-specific contexts.

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INTRODUCTION: the development of this research is base on the growing interest in understanding the adaptations to chronic hipoxia mainly in the range of intermediate altitudes (1 500-3 000 m.s.n.m) and the need to establish parameters of normality in the variables [Hb], Hct and SO2 for diagnostic and characterization of the population purposes. OBJECTIVE: to analyze the behavior of the [Hb], Hct and SaO2 at different intermediate altitudes (970 m.s.n.m, 1 520 m.s.n.m, 1 728 m.s.n.m, 1 923 m.s.n.m, 2 180 m.s.n.m and 2 600 m.s.n.m) in order to contribute to the knowledge of the high altitude physiology and the clinical field to support the diagnosis of anemia. METHODS: clinically healthy subjects with low levels of physical activity and food consumption report containing iron. Total of 264 participants of both genders between 18 and 30 years. The blood samples were collected from the antecubital vein and the earlobe and analyzed in a radiometer. A non-parametric statistical analysis was performed. RESULTS: with increasing of altitude, [Hb] and Hct values were increased while the SO2 decreased. Men showed higher values than women in [Hb] and Hct, related to lower values of SO2 than women. DISCUSSION: a threshold variable was not found, perhaps because of the small distance between the altitudes. The values reported were similar but not identical to other studies. This difference could be explained by genetic diversity among populations. CONCLUSIONS: this study allows for the first values of characterization of the study population. All altitudes were above the cutoff for the diagnosis of anemia ([Hb] 12 g/dl).

Introducción: el desarrollo de la presente investigación se basa en el creciente interés por comprender las adaptaciones a la hipoxia crónica, principalmente en el rango altitudinal denominado de alturas intermedias (1.500- 3.000 m.s.n.m), con la necesidad de establecer parámetros de normalidad en las variables [Hb], Hct y SO2 con fines diagnósticos y de caracterización de la población. Objetivos: analizar el comportamiento de la [Hb], el Hct y la SaO2 a diferentes alturas intermedias (970 m.s.n.m, 1.520 m.s.n.m, 1.728 m.s.n.m, 1.923 m.s.n.m, 2.180 m.s.n.m y 2.600 m.s.n.m) con el fin de aportar conocimiento sobre la fisiología de la altura y al campo clínico para apoyar el diagnóstico de anemia. Métodos: sujetos clínicamente sanos, con nivel bajo de actividad física y reporte de consumo de alimentos con contenido de hierro. Total de 264 participantes de ambos géneros entre 18 y 30 años. Las muestras se obtuvieron de sangre de la vena antecubital y del lóbulo de la oreja y fueron analizadas en un radiómetro. Se realizó un análisis estadístico no paramétrico. Resultados: con el incremento de la altitud los valores de [Hb] y Hct se incrementaron, mientras la SO2 descendió. Los hombres presentaron valores más altos que las mujeres en [Hb] y Hct, relacionado con valores más bajo de SO2 que las mujeres. Discusión: no se evidenció un umbral de las variables, quizás por la pequeña distancia entre las alturas. Los valores reportados fueron similares pero no iguales a otros estudios, lo que podría deberse a la diversidad genética entre poblaciones. Conclusiones: este estudio permite obtener los primeros valores de caracterización de la población estudiada. Todas las alturas estuvieron por encima del punto de corte para el diagnóstico de anemia ([Hb] 12 g/dl).

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