Hox Targets and Cellular Functions

Hox genes are a group of genes that specify structures along the anteroposterior axis in bilaterians. Although in many cases they do so by modifying a homologous structure with a different (or no) Hox input, there are also examples of Hox genes constructing new organs with no homology in other regions of the body. Hox genes determine structures though the regulation of targets implementing cellular functions and by coordinating cell behavior. The genetic organization to construct or modify a certain organ involves both a genetic cascade through intermediate transcription factors and a direct regulation of targets carrying out cellular functions. In this review I discuss new data from genome-wide techniques, as well as previous genetic and developmental information, to describe some examples of Hox regulation of different cell functions. I also discuss the organization of genetic cascades leading to the development of new organs, mainly using Drosophila melanogaster as the model to analyze Hox function

Critical role for Fat/Hippo and IIS/Akt pathways downstream of Ultrabithorax during haltere specification in Drosophila

© 2015 Elsevier Ireland Ltd. In Drosophila, differential development of wing and haltere, which differ in cell size, number and morphology, is dependent on the function of Hox gene Ultrabithorax (Ubx). Here we report our studies on Ubx-mediated regulation of the Fat/Hippo and IIS/dAkt pathways, which control cell number and cell size during development. Over-expression of Yki or down regulation of negative components of the Fat/Hippo pathway, such as expanded, caused considerable increase in haltere size, mainly due to increase in cell number. These phenotypes were also associated with the activation of Akt pathways in developing haltere. Although activation of Akt alone did not affect the cell size or the organ size, we observed dramatic increase in haltere size when Akt was activated in the background where expanded is down regulated. This was associated with the increase in both cell size and cell number. The organ appeared flatter than wildtype haltere and the trichome morphology and spacing resembled that of wing suggesting homeotic transformations. Thus, our results suggest a link between cellular growth and pattern formation and the final differentiated state of the organ.Indo-Spanish grant from DST, India and Ministry of Science and Innovation, Spain to E.S.H. and L.S.S. and JC Bone National Fellowship to L.S.S.Peer Reviewe

Differential activity of Drosophila Hox genes induces myosin expression and can maintain compartment boundaries

Compartments are units of cell lineage that subdivide territories with different developmental potential. In Drosophila, the wing and haltere discs are subdivided into anterior and posterior (A/P) compartments, which require the activity of Hedgehog, and into dorsal and ventral (D/V) compartments, needing Notch signaling. There is enrichment in actomyosin proteins at the compartment boundaries, suggesting a role for these proteins in their maintenance. Compartments also develop in the mouse hindbrain rhombomeres, which are characterized by the expression of different Hox genes, a group of genes specifying different structures along their main axis of bilaterians. We show here that the Drosophila Hox gene Ultrabithorax can maintain the A/P and D/V compartment boundaries when Hedgehog or Notch signaling is compromised, and that the interaction of cells with and without Ultrabithorax expression induces high levels of non-muscle myosin II. In the absence of Ultrabithorax there is occasional mixing of cells from different segments. We also show a similar role in cell segregation for the Abdominal-B Hox gene. Our results suggest that the juxtaposition of cells with different Hox gene expression leads to their sorting out, probably through the accumulation of non-muscle myosin II at the boundary of the different cell territories. The increase in myosin expression seems to be a general mechanism used by Hox genes or signaling pathways to maintain the segregation of different groups of cells.Peer Reviewe

The elimination of an adult segment by the Hox gene Abdominal-B

Hox gene activity leads to morphological diversity of organs or structures in different species. One special case of Hox function is the elimination of a particular structure. The Abdominal-B Hox gene of Drosophila melanogaster provides an example of such activity, as this gene suppresses the formation of the seventh abdominal segment in the adult. This elimination occurs only in males, and is characteristic of more advanced Diptera. The elimination requires the differential expression or activity of genes that are downstream Abdominal-B, or that work togetherwith it, andwhich regulate cell proliferation or cell extrusion. Here,we reviewthe mechanisms responsible for such elimination and provide some new data on processes taking place within this segment. © 2015 Elsevier Ireland Ltd. All rights reserved.Ministerio de Economía y Competitividad (BFU2008-00632 and BFU2011-26075), the Consolider Program (CSD2007-0008) and an Institutional Grant from the Ramon Areces FoundationPeer Reviewe

The Effect of Fertilization on Growth, in Diameter and Height, of Pinus Caribaea in Plantations of Western Cuba

Existen estudios encaminados a analizar el efecto de la fertilización mineral sobre variables dasométricas en plantaciones productivas. En su mayoría, estos analizan la respuesta de la fertilización a corto plazo. Por ello, la presente investigación estudia la respuesta de la fertilización mineral a largo plazo aplicada de forma fraccionada durante los primeros cinco años de establecida una plantación de Pinus caribaea, en el municipio Viñales, Pinar del Río, Cuba. Se investigó la respuesta al crecimiento, en diámetro y altura, a partir de un diseño de bloques al azar. Se establecieron siete tratamientos diferenciados por las dosis de NPK y regímenes de aplicación, más un tratamiento testigo sin fertilización. Se hicieron mediciones en diferentes edades a 288 árboles con seguimiento durante 41 años y se estimaron las funciones de crecimiento mediante regresión multinivel para todo el período, y en dos etapas por separado. Como promedio, en el período de 2 a 41 años, el diámetro en árboles individuales, para las aplicaciones de 600 g árbol-1 en régimen alterno, 800 g árbol-1 y 1000 g árbol-1de (NPK) fueron superiores con respecto al testigo y la altura para las aplicaciones de 800 g árbol-1 y 1000 g árbol-1 de (NPK); el tratamiento de la aplicación de una dosis única de 300 g árbol-1 de (NPK) provocó valores inferiores en diámetro y altura con respecto al testigo. El estudio en dos etapas demostró que de 33 a 41 años se logra homogeneidad en altura entre tratamientos, excepto en el de 300 g árbol-1 de (NPK) que mantiene resultados inferiores al testigo

Convenient synthesis of C75, an inhibitor of FAS and CPT1

C75 is a synthetic racemic α-methylene-γ-butyrolactone exhibiting anti-tumoral properties in vitro and in vivo as well as inducing hypophagia and weight loss in rodents. These interesting properties are thought to be a consequence of the inhibition of the key enzymes FAS and CPT1 involved in lipid metabolism. The need for larger amounts of this compound for biological evaluation prompted us to develop a convenient and reliable route to multigram quantities of C75 from easily available ethyl penta-3,4-dienoate 6. A recently described protocol for the addition of 6 to a mixture of dicyclohexylborane and nonanal followed by acidic treatment of the crude afforded lactone 8, as a mixture of cis and trans isomers, in good yield. The DBU-catalyzed isomerization of the methyl esters 9 arising from 8 gave a 10:1 trans/cis mixture from which the trans isomer was isolated and easily transformed into C75. The temporary transformation of C75 into a phenylseleno ether derivative makes its purification, manipulation and storage easier

On-line breath analysis of volatile organic compounds as a method for colorectal cancer detection

Background: Analysis of exhaled volatile organic compounds (VOCs) in breath is an emerging approach for cancer diagnosis, but little is known about its potential use as a biomarker for colorectal cancer (CRC). We investigated whether a combination of VOCs could distinct CRC patients from healthy volunteers. Methods: In a pilot study, we prospectively analyzed breath exhalations of 38 CRC patient and 43 healthy controls all scheduled for colonoscopy, older than 50 in the average-risk category. The samples were ionized and analyzed using a Secondary ElectroSpray Ionization (SESI) coupled with a Time-of-Flight Mass Spectrometer (SESI-MS). After a minimum of 2 hours fasting, volunteers deeply exhaled into the system. Each test requires three soft exhalations and takes less than ten minutes. No breath condensate or collection are required and VOCs masses are detected in real time, also allowing for a spirometric profile to be analyzed along with the VOCs. A new sampling system precludes ambient air from entering the system, so background contamination is reduced by an overall factor of ten. Potential confounding variables from the patient or the environment that could interfere with results were analyzed. Results: 255 VOCs, with masses ranging from 30 to 431 Dalton have been identified in the exhaled breath. Using a classification technique based on the ROC curve for each VOC, a set of 9 biomarkers discriminating the presence of CRC from healthy volunteers was obtained, showing an average recognition rate of 81.94%, a sensitivity of 87.04% and specificity of 76.85%. Conclusions: A combination of cualitative and cuantitative analysis of VOCs in the exhaled breath could be a powerful diagnostic tool for average-risk CRC population. These results should be taken with precaution, as many endogenous or exogenous contaminants could interfere as confounding variables. On-line analysis with SESI-MS is less time-consuming and doesn’t need sample preparation. We are recruiting in a new pilot study including breath cleaning procedures and spirometric analysis incorporated into the postprocessing algorithms, to better control for confounding variables

Sharp boundaries of Dpp signalling trigger local cell death required for Drosophila leg morphogenesis

Article available at http://dx.doi.org/10.1038/ncb1518Morphogens are secreted signalling molecules that govern many developmental processes1. In the Drosophila wing disc, the transforming growth factor (TGF) homologue Decapentaplegic (Dpp) forms a smooth gradient and specifies cell fate by conferring a defined value of morphogen activity. Thus, neighbouring cells have similar amounts of Dpp protein, and if a sharp discontinuity in Dpp activity is generated between these cells, Jun kinase (JNK)-dependent apoptosis is triggered to restore graded positional information2, 3. To date, it has been assumed that this apoptotic process is only activated when normal signalling is distorted. However, we now show that a similar process occurs during normal development: rupture in Dpp activity occurs during normal segmentation of the distal legs of Drosophila. This sharp boundary of Dpp signalling, independently of the absolute level of Dpp activity, induces a JNK—reaper-dependent apoptosis required for the morphogenesis of a particular structure of the leg, the joint. Our results show that Dpp could induce a developmental programme not only in a concentration dependent manner, but also by the creation of a sharp boundary of Dpp activity. Furthermore, the same process could be used either to restore a normal pattern in response to artificial disturbance or to direct a morphogenetic process.This work has been supported by grants from the Dirección General de Investigación Científica y Técnica (BMC 2002-00300), the Comunidad Autónoma de Madrid (08.1/0031/2001.1 and GR/SAL/0147/2004) and an Institutional Grant from the Fundación Ramón Areces. C.M. is a recipient of a Formación del Personal Universitario (F.P.U.) fellowship from the Ministerio de Educación y Ciencia.Peer reviewe