Henrike Donner (Ed.). Being Middle Class in India: A Way of Life. New York: Routledge, 2011

Book review

The T-box family

Transcription factors of the T-box family are required both for early cell-fate decisions, such as those necessary for formation of the basic vertebrate body plan, and for differentiation and organogenesis. When mutated, T-box genes give dramatic phenotypes in mouse and zebrafish, and they have been implicated both in fundamentals of limb patterning and in a number of human congenital malformations such as Holt-Oram, ulnar-mammary and DiGeorge syndromes, as well as being amplified in a subset of cancers. Genes encoding members of the T-box family have recently been shown to comprise approximately 0.1% of genomes as diverse as those of nematodes and humans and have been identified in a wide variety of animals from ctenophores (comb jellies) to mammals; they are, however, completely absent from genomes from other organisms (such as the model plant Arabidopsis thaliana)

Vertebrate CASTOR Is Required for Differentiation of Cardiac Precursor Cells at the Ventral Midline

SummaryThe CASTOR (CST) transcription factor was initially identified for its role in maintaining stem cell competence in the Drosophila dorsal midline. Here we report that Xenopus CST affects cardiogenesis. In CST-depleted embryos, cardiomyocytes at the ventral midline arrest and are maintained as cardiac progenitors, while cells in more dorsal regions of the heart undergo their normal program of differentiation. Cardia bifida results from failed midline differentiation, even though cardiac cell migration and initial cell fate specification occur normally. Our fate mapping studies reveal that this ventral midline population of cardiomyocytes ultimately gives rise to the outer curvature of the heart; however, CST-depleted midline cells overproliferate and remain a coherent population of nonintegrated cells positioned on the outer wall of the ventricle. These midline-specific requirements for CST suggest the regulation of cardiomyocyte differentiation is regionalized along a dorsal-ventral axis and that this patterning occurs prior to heart tube formation

Vertebrate CASTOR Is Required for Differentiation of Cardiac Precursor Cells at the Ventral Midline

SummaryThe CASTOR (CST) transcription factor was initially identified for its role in maintaining stem cell competence in the Drosophila dorsal midline. Here we report that Xenopus CST affects cardiogenesis. In CST-depleted embryos, cardiomyocytes at the ventral midline arrest and are maintained as cardiac progenitors, while cells in more dorsal regions of the heart undergo their normal program of differentiation. Cardia bifida results from failed midline differentiation, even though cardiac cell migration and initial cell fate specification occur normally. Our fate mapping studies reveal that this ventral midline population of cardiomyocytes ultimately gives rise to the outer curvature of the heart; however, CST-depleted midline cells overproliferate and remain a coherent population of nonintegrated cells positioned on the outer wall of the ventricle. These midline-specific requirements for CST suggest the regulation of cardiomyocyte differentiation is regionalized along a dorsal-ventral axis and that this patterning occurs prior to heart tube formation

Cellular and molecular mechanisms underlying blood vessel lumen formation

The establishment of a functional vascular system requires multiple complex steps throughout embryogenesis, from endothelial cell (EC) specification to vascular patterning into venous and arterial hierarchies. Following the initial assembly of ECs into a network of cord-like structures, vascular expansion and remodeling occur rapidly through morphogenetic events including vessel sprouting, fusion, and pruning. In addition, vascular morphogenesis encompasses the process of lumen formation, critical for the transformation of cords into perfusable vascular tubes. Studies in mouse, zebrafish, frog, and human endothelial cells have begun to outline the cellular and molecular requirements underlying lumen formation. Although the lumen can be generated through diverse mechanisms, the coordinated participation of multiple conserved molecules including transcription factors, small GTPases, and adhesion and polarity proteins remains a fundamental principle, leading us closer to a more thorough understanding of this complex event

Emerging Field of Cardiomics: High-Throughput Investigations into Transcriptional Regulation of Cardiovascular Development and Disease

Congenital heart defects remain a leading cause of infant mortality in the western world, despite decades of research focusing on cardiovascular development and disease,. With the recent emergence of several high-throughput technologies including RNA sequencing, chromatin immunoprecipitation-coupled sequencing, mass spectrometry-based proteomics analyses, and the numerous variations of these strategies, investigations into cardiac development have been transformed from candidate-based studies into whole-genome, -transcriptome, and -proteome undertakings. In this review, we discuss several reports that have emerged from our lab and others over the last five years that emphasize the versatility of large dataset-based investigations of cardiogenic transcription factors, from phenotypic validations and new gene implications to the identification of novel roles of well-studied transcriptional regulators

Expanding the genetic toolkit in Xenopus : approaches and opportunities for human disease modeling

© The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Developmental Biology 426 (2017): 325-335, doi:10.1016/j.ydbio.2016.04.009.The amphibian model Xenopus, has been used extensively over the past century to study multiple aspects of cell and developmental biology. Xenopus offers advantages of a non-mammalian system, including high fecundity, external development, and simple housing requirements, with additional advantages of large embryos, highly conserved developmental processes, and close evolutionary relationship to higher vertebrates. There are two main species of Xenopus used in biomedical research, Xenopus laevis and Xenopus tropicalis; the common perception is that both species are excellent models for embryological and cell biological studies, but only Xenopus tropicalis is useful as a genetic model. The recent completion of the Xenopus laevis genome sequence combined with implementation of genome editing tools, such as TALENs (transcription activator-like effector nucleases) and CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR associated nucleases), greatly facilitates the use of both Xenopus laevis and Xenopus tropicalis for understanding gene function in development and disease. In this paper, we review recent advances made in Xenopus laevis and Xenopus tropicalis with TALENs and CRISPR-Cas and discuss the various approaches that have been used to generate knockout and knock-in animals in both species. These advances show that both Xenopus species are useful for genetic approaches and in particular counters the notion that Xenopus laevis is not amenable to genetic manipulations.This work was supported by the National Institutes of Health (P40 OD010997 to M.E.H., R01 HD084409 to M.E.H., R01 HL112618 to P.T. and F.C., and R01 HL127640 to P.T. and F.C.; and the U.S. Environmental Protection Agency (G11E10367 to D.F.)

The Lhx9-integrin pathway is essential for positioning of the proepicardial organ

The development of the vertebrate embryonic heart occurs by hyperplastic growth as well as the incorporation of cells from tissues outside of the initial heart field. Amongst these tissues is the epicardium, a cell structure that develops from the precursor proepicardial organ on the right side of the septum transversum caudal to the developing heart. During embryogenesis, cells of the proepicardial organ migrate, adhere and envelop the maturing heart, forming the epicardium. The cells of the epicardium then delaminate and incorporate into the heart giving rise to cardiac derivatives, including smooth muscle cells and cardiac fibroblasts. Here, we demonstrate that the LIM homeodomain protein Lhx9 is transiently expressed in Xenopus proepicardial cells and is essential for the position of the proepicardial organ on the septum transversum. Utilizing a small-molecule screen, we found that Lhx9 acts upstream of integrin-paxillin signaling and consistently demonstrate that either loss of Lhx9 or disruption of the integrin-paxillin pathway results in mis-positioning of the proepicardial organ and aberrant deposition of extracellular matrix proteins. This leads to a failure of proepicardial cell migration and adhesion to the heart, and eventual death of the embryo. Collectively, these studies establish a requirement for the Lhx9-integrin-paxillin pathway in proepicardial organ positioning and epicardial formation