Geometric Morphometrics on Gene Expression Patterns Within Phenotypes: A Case Example on Limb Development.

How the genotype translates into the phenotype through development is critical to fully understand the evolution of phenotypes. We propose a novel approach to directly assess how changes in gene expression patterns are associated with changes in morphology using the limb as a case example. Our method combines molecular biology techniques, such as whole-mount in situ hybridization, with image and shape analysis, extending the use of Geometric Morphometrics to the analysis of nonanatomical shapes, such as gene expression domains. Elliptical Fourier and Procrustes-based semilandmark analyses were used to analyze the variation and covariation patterns of the limb bud shape with the expression patterns of two relevant genes for limb morphogenesis, Hoxa11 and Hoxa13. We devised a multiple thresholding method to semiautomatically segment gene domains at several expression levels in large samples of limb buds from C57Bl6 mouse embryos between 10 and 12 postfertilization days. Besides providing an accurate phenotyping tool to quantify the spatiotemporal dynamics of gene expression patterns within developing structures, our morphometric analyses revealed high, non-random, and gene-specific variation undergoing canalization during limb development. Our results demonstrate that Hoxa11 and Hoxa13, despite being paralogs with analogous functions in limb patterning, show clearly distinct dynamic patterns, both in shape and size, and are associated differently with the limb bud shape. The correspondence between our results and already well-established molecular processes underlying limb development confirms that this morphometric approach is a powerful tool to extract features of development regulating morphogenesis. Such multilevel analyses are promising in systems where not so much molecular information is available and will advance our understanding of the genotype-phenotype map. In systematics, this knowledge will increase our ability to infer how evolution modified a common developmental pattern to generate a wide diversity of morphologies, as in the vertebrate limb.

[Orthotopic renal allograft transplant. State of the art.] / Trasplante renal ortotópico. Estado actual.

Kidney transplantation is the treatment of choice for patients with end-stage renal disease (ESRD)as it has shown a better quality of life and longer survival compared to dialysis. Patients with ESRD have associated vascular pathology in a significant percentage, with abundant calcifications at the level of the aorto-iliac axis.The survival of transplanted patients has also increased so an important number of patients have multiple transplants,patients with an indication for a third, fourth and even fifth transplant.In these cases, in which the iliac fossa is no longer practicable(atheromatosis, vascular abnormalities, occupied iliac fossae for previous kidney transplant…), orthotopic kidney transplantation offers a viable option with good results.

El trasplante renal es el tratamiento de elección para pacientes con insuficiencia renal crónica terminal (IRCT) ya que ha demostrado una mejor calidadd e vida y mayor supervivencia en comparación ala diálisis. Los pacientes con IRCT tienen asociada patología vascular en un importante porcentaje, con abundantes calcificaciones a nivel del eje aorto-ilíaco. La supervivencia de los pacientes trasplantados también se ha incrementado por lo que cada vez más nos encontramos con pluritrasplantados, pacientes con indicación de tercer, cuarto e incluso quinto trasplante.En estos casos en los que la fosa ilíaca ya no es practicable (ateromatosis, malformaciones vasculares, ocupación de fosas ilíacas por trasplantes renales previos…),el trasplante renal ortotópico ofrece una opción viable con buenos resultados.

Trasplante renal ortotópico. Estado actual / Trapianto renale ortotopico. Stato attuale

El trasplante renal es el tratamiento deelección para pacientes con insuficiencia renal crónicaterminal (IRCT) ya que ha demostrado una mejor calidad de vida y mayor supervivencia en comparación ala diálisis. Los pacientes con IRCT tienen asociada patología vascular en un importante porcentaje, con abundantes calcificaciones a nivel del eje aorto-ilíaco. Lasupervivencia de los pacientes trasplantados también seha incrementado por lo que cada vez más nos encontramos con pluritrasplantados, pacientes con indicaciónde tercer, cuarto e incluso quinto trasplante.En estos casos en los que la fosa ilíaca ya no es practicable (ateromatosis, malformaciones vasculares, ocupación de fosas ilíacas por trasplantes renales previos...),el trasplante renal ortotópico ofrece una opción viablecon buenos resultados.(AU)

Kidney transplantation is the treatment ofchoice for patients with end-stage renal disease (ESRD)as it has shown a better quality of life and longer survivalcompared to dialysis. Patients with ESRD have associated vascular pathology in a significant percentage, withabundant calcifications at the level of the aorto-iliac axis.The survival of transplanted patients has also increasedso an important number of patients have multiple transplants, patients with an indication for a third, fourth andeven fifth transplant.In these cases, in which the iliac fossa is no longer practicable (atheromatosis, vascular abnormalities, occupiediliac fossae for previous kidney transplant...) , orthotopickidney transplantation offers a viable option with goodresults.(AU)