Trends in developmental biology最新文献

The life-sustaining air-blood interface of the respiratory system requires the exquisite integration of the epithelial lining with the mesenchymal capillary network, all supported by elastic smooth muscle and rigid cartilage keeping the expandable airways open. These intimate tissue interactions originate in the early embryo, where bidirectional paracrine signaling between the endoderm epithelium and adjacent mesoderm orchestrates lung and trachea development and controls the stereotypical branching morphogenesis. Although much attention has focused on how these interactions impact the differentiation of the respiratory epithelium, relatively less is known about the patterning and differentiation of the mesenchyme. Endothelial cells, smooth muscle cells, and chondrocytes together with other types of mesenchymal cells are essential components of a functional respiratory system, and malformation of these cells can lead to various congenital defects. In this review, we summarize the current understanding of mesenchymal development in the fetal trachea and lung, focusing on recent findings from animal models that have begun to shed light on the poorly understood respiratory mesenchyme lineages.

A satellite symposium to the Canadian Developmental Biology Conference 2016 was held on March 16-17, 2016 in Banff, Alberta, Canada, entitled Forebrain Neurogenesis: From embryo to adult. The Forebrain Neurogenesis symposium was a focused, high-intensity meeting, bringing together the top Canadian and international researchers in the field. This symposium reported the latest breaking news, along with 'state of the art' techniques to answer fundamental questions in developmental neurobiology. Topics covered ranged from stem cell regulation to neurocircuitry development, culminating with a session focused on neuropsychiatric disorders. Understanding the underlying causes of neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) is of great interest as diagnoses of these conditions are climbing at alarming rates. For instance, in 2012, the Centers for Disease Control reported that the prevalence rate of ASD in the U.S. was 1 in 88; while more recent data indicate that the number is as high as 1 in 68 (Centers for Disease Control and Prevention MMWR Surveillance Summaries. Vol. 63. No. 2). Similarly, the incidence of ASD is on the rise in Canada, increasing from 1 in 150 in 2000 to 1 in 63 in 2012 in southeastern Ontario (Centers for Disease Control and Prevention). Currently very little is known regarding the deficits underlying these neurodevelopmental conditions. Moreover, the development of effective therapies is further limited by major gaps in our understanding of the fundamental processes that regulate forebrain development and adult neurogenesis. The Forebrain Neurogenesis satellite symposium was thus timely, and it played a key role in advancing research in this important field, while also fostering collaborations between international leaders, and inspiring young researchers.

All vertebrate eggs are surrounded by an extracellular coat that supports growth of oocytes, protects oocytes, eggs, and early embryos, and participates in the process of fertilization. In mammals (platypus to human beings) the coat is called a zona pellucida (ZP) and in non-mammals (molluscs to birds), a vitelline envelope (VE). The ZP and VE are composed of just a few proteins that are related to one another and possess a common motif, called the zona pellucida domain (ZPD). The ZPD arose more than ~600 million years ago, consists of ~260 amino acids, and has 8 conserved Cys residues that participate in 4 intramolecular disulfides. It is likely that egg-coat proteins are derived from a common ancestral gene. This gene duplicated several times during evolution and gave rise to 3-4 genes in fish, 5 genes in amphibians, 6 genes in birds, and 3-4 genes in mammals. Some highly divergent sequences, N- and C-terminal to the ZPD, have been identified in egg-coat proteins and some of these sequences may be under positive Darwinian selection that drives evolution of the proteins. These and other aspects of egg-coat proteins, including their structure and synthesis, are addressed in this review.

Perhaps development is more than just morphogenesis. We now recognize that the conceptus expresses epigenetic marks that heritably affect it phenotypically, indicating that the offspring are to some degree genetically autonomous, and that ontogeny and phylogeny may coordinately determine the fate of such marks. This scenario mechanistically links ecology, ontogeny and phylogeny together as an integrated mechanism for evolution for the first time. As a functional example, the Parathyroid Hormone-related Protein (PTHrP) signaling duplicated during the Phanerozoic water-land transition. The PTHrP signaling pathway was critical for the evolution of the skeleton, skin barrier, and lung function, based on experimental evidence, inferring that physiologic stress can profoundly affect adaptation through internal selection, giving seminal insights to how and why vertebrates were able to evolve from water to land. By viewing evolution from its inception in unicellular organisms, driven by competition between pro- and eukaryotes, the emergence of complex biologic traits from the unicellular cell membrane offers a novel way of thinking about the process of evolution from its beginnings, rather than from its consequences as is traditionally done. And by focusing on the epistatic balancing mechanisms for calcium and lipid homeostasis, the evolution of unicellular organisms, driven by competition between pro- and eukaryotes, gave rise to the emergence of complex biologic traits derived from the unicellular plasma lemma, offering a unique way of thinking about the process of evolution. By exploiting the cellular-molecular mechanisms of lung evolution as ontogeny and phylogeny, the sequence of events for the evolution of the skin, kidney and skeleton become more transparent. This novel approach to the evolution question offers equally novel insights to the primacy of the unicellular state, hologenomics and even a priori bioethical decisions.

The circulatory system is the first hierarchically ordered network to form during the development of vertebrates as it is an indispensable means of adequate oxygen and nutrient delivery to developing organs. During the initial phase of vascular development, endothelial lineage-committed cells differentiate, migrate, and coalesce to form the central large axial vessels and their branches. The subsequent phase of vessel expansion (i.e., angiogenesis) involves a cascade of events including endothelial cell migration, proliferation, formation of an immature capillary structure, recruitment of mural cells and deposition of a basement membrane to yield a functional vasculature. These series of events are tightly regulated by the coordinated expression of several angiogenic, morphogenic and guidance factors. The extracellular matrix (ECM) is synthesized and secreted by embryonic cells at the earliest stages of development and forms a pericellular network of bioactive stimulatory and inhibitory angiogenesis regulatory factors. Here we describe the role of a subset of inducible immediate-early gene-encoded, ECM-associated integrin- and heparin-binding proteins referred to as CCN1 (or Cyr61) and CCN2 (or CTGF) and their function in the development of the vascular system. Gene-targeting experiments in mice have identified CCN1 and CCN2 as critical rate-limiting determinants of endothelial cell differentiation and quiescence, mural cell recruitment and basement membrane formation during embryonic vascular development. Emphasis will be placed on the regulation and function of these molecules and their contextual mode of action during vascular development. Further understanding of the mechanisms of CCN1- and CCN2-mediated blood vessel expansion and remodeling would enhance the prospects that these molecules provide for the development of new treatments for vascular diseases.

In the inner ear, Notch signaling has been shown to have two key developmental roles. The first occurs early in otic development and defines the prosensory domains that will develop into the six sensory organs of the inner ear. The second role occurs later in development and establishes the mosaic-like pattern of the mechanosensory hair cells and their surrounding support cells through the more well-characterized process of lateral inhibition. These dual developmental roles have inspired several different strategies to regenerate hair cells in the mature inner ear organs. These strategies include (1) modulation of Notch signaling in inner ear stem cells in order to increase hair cell yield, (2) activation of Notch signaling in order to promote the formation of ectopic sensory regions in normally non-sensory regions within the inner ear, and (3) inhibition of Notch signaling to disrupt lateral inhibition and allow support cells to transdifferentiate into hair cells. In this review, we summarize some of the promising studies that have used these various strategies for hair cell regeneration through modulation of Notch signaling and some of the challenges that remain in developing therapies based on hair cell regeneration.

Skeletogenesis is a complex multi-step process, which involves many genes and pathways. The tightly regulated interplay between these genes in these pathways ensures a correct and timely organogenesis and it is imperative that we have a fair understanding of the major genes and gene families involved in the process. This review aims to give a deeper insight into the roles of 3 major transcription factor families involved in skeleton formation: Sox, Runx and Pax and to look at the human skeleotogenic phenotypes associated with mutations in these genes.