Birth Defects Research Part C-Embryo Today-Reviews最新文献

Orofacial clefts, including cleft palates (CP), are one of the most common birth defects. CP have a multiplicity of effects on the individual and society in terms of economic costs, loss of productivity, psychosocial effects, and increased morbidity and mortality at all stages of life. Embryological development of the palate is well delineated, with developments in the last decade regarding the biomolecular processes involved. Etiology is complex, involving a number of genetic and environmental factors. Various techniques can be employed for the repair of CP, depending on whether the cleft is of the primary or secondary palate, the width of the cleft, whether lengthening of the palate is necessary, and with regard to concerns of disruption of midfacial growth. All surgical techniques have the goals of restoring functional speech, swallowing, and aesthetics. A multidisciplinary team is necessary for the long-term pre- and postoperative care of CP patients to handle complications, associated anomalies, and to optimize function and quality of life. Birth Defects Research (Part C) 102:333–342, 2014. © 2014 Wiley Periodicals, Inc.

The birth of a baby with malformations of the genitalia urges medical action. Even in cases where the condition is not life-threatening, the identification of the external genitalia as male or female is emotionally essential for the family, and genital malformations represent one of the most stressful situations around a newborn. The female or male configuration of the genitalia normally evolves during fetal life according to the genetic, gonadal, and hormonal sex. Disorders of sex development occur when male hormone (androgens and anti-Müllerian hormone) secretion or action is insufficient in the 46,XY fetus or when there is an androgen excess in the 46,XX fetus. However, sex hormone defects during fetal development cannot explain all congenital malformations of the reproductive tract. This review is focused on those congenital conditions in which gonadal function and sex hormone target organ sensitivity are normal and, therefore, not responsible for the genital malformation. Furthermore, because the reproductive and urinary systems share many common pathways in embryo-fetal development, conditions associating urogenital malformations are discussed. Birth Defects Research (Part C) 102:359–373, 2014. © 2014 Wiley Periodicals, Inc.

Pulmonary vascular diseases of the newborn comprise a wide range of pathological conditions with developmental abnormalities in the pulmonary vasculature. Clinically, pulmonary arterial hypertension (PH) is characterized by persistent increased resistance of the vasculature and abnormal vascular response. The classification of PH is primarily based on clinical parameters instead of morphology and distinguishes five groups of PH. Congenital lung anomalies, such as alveolar capillary dysplasia (ACD) and PH associated with congenital diaphragmatic hernia (CDH), but also bronchopulmonary dysplasia (BPD), are classified in group three. Clearly, tight and correct regulation of pulmonary vascular development is crucial for normal lung development. Human and animal model systems have increased our knowledge and make it possible to identify and characterize affected pathways and study pivotal genes. Understanding of the normal development of the pulmonary vasculature will give new insights in the origin of the spectrum of rare diseases, such as CDH, ACD, and BPD, which render a significant clinical problem in neonatal intensive care units around the world. In this review, we describe normal pulmonary vascular development, and focus on four diseases of the newborn in which abnormal pulmonary vascular development play a critical role in morbidity and mortality. In the future perspective, we indicate the lines of research that seem to be very promising for elucidating the molecular pathways involved in the origin of congenital pulmonary vascular disease. Birth Defects Research (Part C) 102:343–358, 2014. © 2014 Wiley Periodicals, Inc.

Congenital anomalies of the kidney and urinary tract (CAKUT) represent a broad range of disorders that result from abnormalities of the urinary collecting system, abnormal embryonic migration of the kidneys, or abnormal renal parenchyma development. These disorders are commonly found in humans, accounting for 20–30% of all genetic malformations diagnosed during the prenatal period. It has been estimated that CAKUT are responsible for 30–50% of all children with chronic renal disease worldwide and that some anomalies can predispose to adult-onset diseases, such as hypertension. Currently, there is much speculation regarding the pathogenesis of CAKUT. Common genetic background with variable penetrance plays a role in the development of the wide spectrum of CAKUT phenotypes. This review aims to summarize the possible mechanisms by which genes responsible for kidney and urinary tract morphogenesis might be implicated in the pathogenesis of CAKUT. Birth Defects Research (Part C) 102:374–381, 2014. © 2014 Wiley Periodicals, Inc.

Neural crest cells are multipotent cells, which are specified in embryonic ectoderm in the border of neural plate and epiderm during early development by interconnection of extrinsic stimuli and intrinsic factors. Neural crest cells are capable of differentiating into various somatic cell types, including melanocytes, craniofacial cartilage and bone, smooth muscle, and peripheral nervous cells, which supports their promise for cell therapy. In this work, we provide a comprehensive review of wide aspects of neural crest cells from their developmental biology to applicability in medical research. We provide a simplified model of neural crest cell development and highlight the key external stimuli and intrinsic regulators that determine the neural crest cell fate. Defects of neural crest cell development leading to several human disorders are also mentioned, with the emphasis of using human induced pluripotent stem cells to model neurocristopathic syndromes. Birth Defects Research (Part C) 102:263–274, 2014. © 2014 Wiley Periodicals, Inc.

This review provides an overview of the state and future directions of development and pathology in the craniofacial complex in the context of Cranial Neural Crest Cells (CNCC). CNCC are a multipotent cell population that is largely responsible for forming the vertebrate head. We focus on findings that have increased the knowledge of gene regulatory networks and molecular mechanisms governing CNCC migration and the participation of these cells in tissue formation. Pathology due to aberrant migration or cell death of CNCC, termed neurocristopathies, is discussed in addition to craniosynostoses. Finally, we discuss tissue engineering applications that take advantage of recent advancements in genome editing and the multipotent nature of CNCC. These applications have relevance to treating diseases due directly to the failure of CNCC, and also in restoring tissues lost due to a variety of reasons. Birth Defects Research (Part C) 102:324–332, 2014. © 2014 Wiley Periodicals, Inc.

Whether it is due to a particular epigenetic signature, or some other component of an embryonic differentiation program, accumulating evidence indicates that the origins of a stem cell has a profound impact on the potential of a tissue to regenerate and repair. Here, we focus on Müller glia, long considered the stem cells of the retina, and their surprising derivation from the neural crest. Whether the multipotent properties of a subset of Müller glia is associated with their neural crest origin remains a tantalizing possibility. Birth Defects Research (Part C) 102:299–308, 2014. © 2014 Wiley Periodicals, Inc.

In this review article I explore the suitability of human epidermal neural crest stem cells (hEPI-NCSC) for translational medicine. hEPI-NCSC are multipotent somatic stem cells that are derived from the embryonic neural crest. hEPI-NCSC are located in the bulge of hair follicles where they persist postnatally and into adulthood. Because of their location in the hairy skin and their migratory behavior, hEPI-NCSC can be easily isolated as a highly pure population of stem cells without the need for purification. Furthermore they can be expanded ex vivo into millions of stem cells, they do not form tumors in vivo, and they can undergo directed differentiation into crest and noncrest-derived cell types of clinical relevance. Taken together, these characteristics make hEPI-NCSC attractive candidates for cell-based therapies, drug discovery, and disease modeling. Birth Defects Research (Part C) 102:221–226, 2014. © 2014 Wiley Periodicals, Inc.

The cardiac neural crest cells (CNCCs) have played an important role in the evolution and development of the vertebrate cardiovascular system: from reinforcement of the developing aortic arch arteries early in vertebrate evolution, to later orchestration of aortic arch artery remodeling into the great arteries of the heart, and finally outflow tract septation in amniotes. A critical element necessary for the evolutionary advent of outflow tract septation was the co-evolution of the cardiac neural crest cells with the second heart field. This review highlights the major transitions in vertebrate circulatory evolution, explores the evolutionary developmental origins of the CNCCs from the third stream cranial neural crest, and explores candidate signaling pathways in CNCC and outflow tract evolution drawn from our knowledge of DiGeorge Syndrome. Birth Defects Research (Part C) 102:309–323, 2014. © 2014 Wiley Periodicals, Inc.