A Novel Perspective on Neuronal Control of Anatomical Patterning, Remodeling, and Maintenance.

While the nervous system may be best known as the sensory communication center of an organism, recent research has revealed a myriad of multifaceted roles for both the CNS and PNS from early development to adult regeneration and remodeling. These systems work to orchestrate tissue pattern formation during embryonic development and continue shaping pattering through transitional periods such as metamorphosis and growth. During periods of injury or wounding, the nervous system has also been shown to influence remodeling and wound healing.

Adaptive correction of craniofacial defects in pre-metamorphic tadpoles involves thyroid hormone-independent tissue remodeling.

Although it is well established that some organisms can regenerate lost structures, the ability to remodel existing malformed structures has been less well studied. Therefore, in this study we examined the ability of pre-metamorphic tadpoles to self-correct malformed craniofacial tissues. We found that tadpoles can adaptively improve and normalize abnormal craniofacial morphology caused by numerous developmental perturbations.

Mechanisms of physiological tissue remodeling in animals: Manipulating tissue, organ, and organism morphology.

Tissue remodeling is broadly defined as the reorganization or restoration of existing tissues. Tissue remodeling processes are responsible for directing the development and maintenance of tissues, organs, and overall morphology of an organism. Therefore, studying the regulatory and mechanistic aspects of tissue remodeling allows one to decipher how tissue structure and function is manipulated in animals.

Recovery of the Xenopus laevis heart from ROS-induced stress utilizes conserved pathways of cardiac regeneration.

Urodele amphibians and some fish are capable of regenerating up to a quarter of their heart tissue after cardiac injury. While many anuran amphibians like Xenopus laevis are not capable of such feats, they are able to repair lesser levels of cardiac damage, such as that caused by oxidative stress, to a far greater degree than mammals. Using an optogenetic stress induction model that utilizes the protein KillerRed, we have investigated the extent to which mechanisms of cardiac regeneration are conserved during the restoration of normal heart morphology post oxidative stress in X.

Bioelectric signaling in regeneration: Mechanisms of ionic controls of growth and form.

The ability to control pattern formation is critical for the both the embryonic development of complex structures as well as for the regeneration/repair of damaged or missing tissues and organs. In addition to chemical gradients and gene regulatory networks, endogenous ion flows are key regulators of cell behavior. Not only do bioelectric cues provide information needed for the initial development of structures, they also enable the robust restoration of normal pattern after injury.

HCN4 ion channel function is required for early events that regulate anatomical left-right patterning in a nodal and lefty asymmetric gene expression-independent manner.

Laterality is a basic characteristic of all life forms, from single cell organisms to complex plants and animals. For many metazoans, consistent left-right asymmetric patterning is essential for the correct anatomy of internal organs, such as the heart, gut, and brain; disruption of left-right asymmetry patterning leads to an important class of birth defects in human patients. Laterality functions across multiple scales, where early embryonic, subcellular and chiral cytoskeletal events are coupled with asymmetric amplification mechanisms and gene regulatory networks leading to asymmetric physical forces that ultimately result in distinct left and right anatomical organ patterning.

Coordinating heart morphogenesis: A novel role for hyperpolarization-activated cyclic nucleotide-gated (HCN) channels during cardiogenesis in .

Hyperpolarization-activated cyclic-nucleotide gated channel (HCN) proteins are important regulators of both neuronal and cardiac excitability. Among the 4 HCN isoforms, HCN4 is known as a pacemaker channel, because it helps control the periodicity of contractions in vertebrate hearts. Although the physiological role of HCN4 channel has been studied in adult mammalian hearts, an earlier role during embryogenesis has not been clearly established.

Use of Xenopus Frogs to Study Renal Development/Repair.

The Xenopus genus includes several members of aquatic frogs native to Africa but is perhaps best known for the species Xenopus laevis and Xenopus tropicalis. These species were popularized as model organisms from as early as the 1800s and have been instrumental in expanding several biological fields including cell biology, environmental toxicology, regenerative biology, and developmental biology. In fact, much of what we know about the formation and maturation of the vertebrate renal system has been acquired by examining the intricate genetic and morphological patterns that epitomize nephrogenesis in Xenopus.

Beyond the Mammalian Heart: Fish and Amphibians as a Model for Cardiac Repair and Regeneration.

The epidemic of heart disease, the leading cause of death worldwide, is made worse by the fact that the adult mammalian heart is especially poor at repair. Damage to the mammal heart-such as that caused by myocardial infarction-leads to scarring, resulting in cardiac dysfunction and heart failure. In contrast, the hearts of fish and urodele amphibians are capable of complete regeneration of cardiac tissue from multiple types of damage, with full restoration of functionality.

Optogenetic Control of Apoptosis in Targeted Tissues of Xenopus laevis Embryos.

KillerRed (KR) is a recently discovered fluorescent protein that, when activated with green light, releases reactive oxygen species (ROS) into the cytoplasm, triggering apoptosis in a KR-expressing cell. This property allows for the use of KR as a means of killing cells in an organism with great temporal and spatial specificity, while minimizing the nonspecific effects that can result from mechanical or chemical exposure damage techniques. Such optogenetic control of cell death, and the resulting ability to induce the targeted death of specific tissues, is invaluable for regeneration/repair studies-particularly in Xenopus laevis, where apoptosis plays a key role in regeneration and repair.

Regeneration of functional pronephric proximal tubules after partial nephrectomy in Xenopus laevis.

Background: While the renal system is critical for maintaining homeostatic equilibrium within the body, it is also susceptible to various kinds of damage. Tubule dysfunction in particular contributes to acute renal injury and chronic kidney disease in millions of patients worldwide. Because current treatments are highly invasive and often unavailable, gaining a better understanding of the regenerative capacity of renal structures is vital.

Low concentrations of atrazine, glyphosate, 2,4-dichlorophenoxyacetic acid, and triadimefon exposures have diverse effects on Xenopus laevis organ morphogenesis.

Many chemicals are released into the environment, and chemical contamination has been suggested as a contributing factor to amphibian declines. To add to a growing body of knowledge about the impact of individual chemicals on non-target organisms, we examined the specificity of deformities induced by exposure to four pesticides (atrazine, 2,4-dichloropheoxyacetic acid (2,4-D), triadimefon, and glyphosate) in the model amphibian species, Xenopus laevis. We focused on the period of organ morphogenesis, as it is frequently found to be particularly sensitive to chemical exposure yet also commonly overlooked.

Acute atrazine exposure disrupts matrix metalloproteinases and retinoid signaling during organ morphogenesis in Xenopus laevis.

Exposure to the herbicide atrazine disrupts many developmental processes in non-target animals. Atrazine exposure during organ morphogenesis in amphibians results in dramatic malformations; the mechanism by which this happens has not been described. We have taken a candidate gene approach to explore two possible mechanisms by which acute atrazine exposure causes extensive malformations in several tissues in Xenopus laevis tadpoles.

Bioelectric controls of cell proliferation: ion channels, membrane voltage and the cell cycle.

All cells possess long-term, steady-state voltage gradients across the plasma membrane. These transmembrane potentials arise from the combined activity of numerous ion channels, pumps and gap junction complexes. Increasing data from molecular physiology now reveal that the role of changes in membrane voltage controls, and is in turn controlled by, progression through the cell cycle.

Coordinating the timing of cardiac precursor development during gastrulation: a new role for Notch signaling.

Notch signaling has been shown to mediate a wide array of cell fate decisions during development. While previous work has demonstrated that Notch signaling plays an important role in regulating cardiac differentiation and morphogenesis, an earlier role during cardiac field formation has not yet been fully characterized. Previously, our lab demonstrated that perturbations in Notch signaling beginning at the onset of gastrulation affect the subdivision of germ layers.

Perturbation of organogenesis by the herbicide atrazine in the amphibian Xenopus laevis.

Background: Exposure to anthropogenic chemicals during development can disrupt the morphogenesis of organ systems. Use of the herbicide atrazine has been debated in recent years because of its implicated, but poorly characterized, effects on vertebrates. Previous studies primarily examined the effects of atrazine exposure during metamorphosis or early developmental stages of amphibians.

Patterning the embryonic kidney: BMP signaling mediates the differentiation of the pronephric tubules and duct in Xenopus laevis.

The Bone morphogenetic proteins (BMPs) mediate a wide range of diverse cellular behaviors throughout development. Previous studies implicated an important role for BMP signaling during the differentiation of the definitive mammalian kidney, the metanephros. In order to examine whether BMP signaling also plays an important role during the patterning of earlier renal systems, we examined the development of the earliest nephric system, the pronephros.

Subdividing the embryo: a role for Notch signaling during germ layer patterning in Xenopus laevis.

The development of all vertebrate embryos requires the establishment of a three-dimensional coordinate system in order to pattern embryonic structures and create the complex shape of the adult organism. During the process of gastrulation, the three primary germ layers are created under the guidance of numerous signaling pathways, allowing cells to communicate during development. Cell-cell communication, mediated by receptors of the Notch family, has been shown to be involved in mediating diverse cellular behaviors during development and has been implicated in the regulation of cell fate decisions in both vertebrate and invertebrate organisms.

The mitochondrial-apoptotic pathway is triggered in Xenopus mesoderm cells deprived of PDGF receptor signaling during gastrulation.

Platelet-derived growth factor receptor (PDGFR) signaling is required for normal gastrulation in Xenopus laevis. Embryos deprived of PDGFR signaling develop with a range of gastrulation-specific defects including spina bifida, shortened anteroposterior axis, and reduced anterior structures. These defects arise because the involuting mesoderm fails to move appropriately.