Inverse-scattering in biological samples via beam-propagation.

Multiple scattering limits optical imaging in thick biological samples by scrambling sample-specific information. Physics-based inverse-scattering methods aim to computationally recover this information, often using non-convex optimization to reconstruct the scatter-corrected sample. However, this non-convexity can lead to inaccurate reconstructions, especially in highly scattering samples.

Facing up to your potential: Neural crest under the influence of TGF-β.

Neural crest cells, an ectoderm derivative, give rise to a variety of cell types. Only in cephalic regions do these cell types include bone and cartilage, which are mesodermal derivatives elsewhere. In this issue of Developmental Cell, Rothstein et al.

DMD and microlens array as a switchable module for illumination angle scanning in optical diffraction tomography.

Optical diffraction tomography (ODT) enables label-free and morphological 3D imaging of biological samples using refractive-index (RI) contrast. To accomplish this, ODT systems typically capture multiple angular-specific scattering measurements, which are used to computationally reconstruct a sample's 3D RI. Standard ODT systems employ scanning mirrors to generate angular illuminations.

Zebrafish raptor mutation inhibits the activity of mTORC1, inducing craniofacial defects due to autophagy-induced neural crest cell death.

The mechanistic target of rapamycin (mTOR) coordinates metabolism and cell growth with environmental inputs. mTOR forms two functional complexes: mTORC1 and mTORC2. Proper development requires both complexes but mTORC1 has unique roles in numerous cellular processes, including cell growth, survival and autophagy.

Divergent cis-regulatory evolution underlies the convergent loss of sodium channel expression in electric fish.

South American and African weakly electric fish independently evolved electric organs from muscle. In both groups, a voltage-gated sodium channel gene independently lost expression from muscle and gained it in the electric organ, allowing the channel to become specialized for generating electric signals. It is unknown how this voltage-gated sodium channel gene is targeted to muscle in any vertebrate.

Variation in phenotypes from a Bmp-Gata3 genetic pathway is modulated by Shh signaling.

We sought to understand how perturbation of signaling pathways and their targets generates variable phenotypes. In humans, GATA3 associates with highly variable defects, such as HDR syndrome, microsomia and choanal atresia. We previously characterized a zebrafish point mutation in gata3 with highly variable craniofacial defects to the posterior palate.

Novel Ethanol-Sensitive Mutants Identified in an F3 Forward Genetic Screen.

Background: Fetal alcohol spectrum disorders (FASD) collectively refer to all deleterious outcomes due to prenatal alcohol exposures. Alterations to the face are common phenotypes in FASD. While alcohol exposure is the underlying cause of FASD, many variables modify the outcomes of such exposures.

In vivo zebrafish morphogenesis shows Cyp26b1 promotes tendon condensation and musculoskeletal patterning in the embryonic jaw.

Integrated development of diverse tissues gives rise to a functional, mobile vertebrate musculoskeletal system. However, the genetics and cellular interactions that drive the integration of muscle, tendon, and skeleton are poorly understood. In the vertebrate head, neural crest cells, from which cranial tendons derive, pattern developing muscles just as tendons have been shown to in limb and trunk tissue, yet the mechanisms of this patterning are unknown.

Bmp signaling mediates endoderm pouch morphogenesis by regulating Fgf signaling in zebrafish.

The endodermal pouches are a series of reiterated structures that segment the pharyngeal arches and help pattern the vertebrate face. Multiple pathways regulate the complex process of endodermal development, including the Bone morphogenetic protein (Bmp) pathway. However, the role of Bmp signaling in pouch morphogenesis is poorly understood.

Role of mef2ca in developmental buffering of the zebrafish larval hyoid dermal skeleton.

Phenotypic robustness requires a process of developmental buffering that is largely not understood, but which can be disrupted by mutations. Here we show that in mef2ca(b1086) loss of function mutant embryos and early larvae, development of craniofacial hyoid bones, the opercle (Op) and branchiostegal ray (BR), becomes remarkably unstable; the large magnitude of the instability serves as a positive attribute to learn about features of this developmental buffering. The OpBR mutant phenotype variably includes bone expansion and fusion, Op duplication, and BR homeosis.

A screen of zebrafish mutants identifies ethanol-sensitive genetic loci.

Background: Fetal alcohol spectrum disorders (FASD) are a highly variable set of phenotypes caused by fetal alcohol exposure. Numerous factors influence FASD phenotypes, including genetics. The zebrafish is a powerful vertebrate model system with which to identify these genetic factors.

Pdgfra protects against ethanol-induced craniofacial defects in a zebrafish model of FASD.

Human birth defects are highly variable and this phenotypic variability can be influenced by both the environment and genetics. However, the synergistic interactions between these two variables are not well understood. Fetal alcohol spectrum disorders (FASD) is the umbrella term used to describe the wide range of deleterious outcomes following prenatal alcohol exposure.

Ahsa1 and Hsp90 activity confers more severe craniofacial phenotypes in a zebrafish model of hypoparathyroidism, sensorineural deafness and renal dysplasia (HDR).

The severity of most human birth defects is highly variable. Our ability to diagnose, treat and prevent defects relies on our understanding of this variability. Mutation of the transcription factor GATA3 in humans causes the highly variable hypoparathyroidism, sensorineural deafness and renal dysplasia (HDR) syndrome.

Bmp and Shh signaling mediate the expression of satb2 in the pharyngeal arches.

In human, mutation of the transcription factor SATB2 causes severe defects to the palate and jaw. The expression and sequence of SATB2 is highly conserved across vertebrate species, including zebrafish. We sought to understand the regulation of satb2 using the zebrafish model system.

Hh signaling regulates patterning and morphogenesis of the pharyngeal arch-derived skeleton.

The proper function of the craniofacial skeleton requires the proper shaping of many individual skeletal elements. Neural crest cells generate much of the craniofacial skeleton and morphogenesis of skeletal elements occurs in transient, reiterated structures termed pharyngeal arches. The shape of individual elements depends upon intrinsic patterning within the neural crest as well as extrinsic signals to the neural crest from adjacent tissues within the arches.

Examination of a palatogenic gene program in zebrafish.

Human palatal clefting is debilitating and difficult to rectify surgically. Animal models enhance our understanding of palatogenesis and are essential in strategies designed to ameliorate palatal malformations in humans. Recent studies have shown that the zebrafish palate, or anterior neurocranium, is under similar genetic control to the amniote palatal skeleton.

Mutations in fam20b and xylt1 reveal that cartilage matrix controls timing of endochondral ossification by inhibiting chondrocyte maturation.

Differentiating cells interact with their extracellular environment over time. Chondrocytes embed themselves in a proteoglycan (PG)-rich matrix, then undergo a developmental transition, termed "maturation," when they express ihh to induce bone in the overlying tissue, the perichondrium. Here, we ask whether PGs regulate interactions between chondrocytes and perichondrium, using zebrafish mutants to reveal that cartilage PGs inhibit chondrocyte maturation, which ultimately dictates the timing of perichondral bone development.

Uhrf1 and Dnmt1 are required for development and maintenance of the zebrafish lens.

DNA methylation is one of the key mechanisms underlying the epigenetic regulation of gene expression. During DNA replication, the methylation pattern of the parent strand is maintained on the replicated strand through the action of Dnmt1 (DNA Methyltransferase 1). In mammals, Dnmt1 is recruited to hemimethylated replication foci by Uhrf1 (Ubiquitin-like, Containing PHD and RING Finger Domains 1).

Zebrafish sp7:EGFP: a transgenic for studying otic vesicle formation, skeletogenesis, and bone regeneration.

We report the expression pattern and construction of a transgenic zebrafish line for a transcription factor involved in otic vesicle formation and skeletogenesis. The zinc finger transcription factor sp7 (formerly called osterix) is reported as a marker of osteoblasts. Using bacterial artificial chromosome (BAC)-mediated transgenesis, we generated a zebrafish transgenic line for studying skeletal development, Tg(sp7:EGFP)b1212.

MicroRNA Mirn140 modulates Pdgf signaling during palatogenesis.

Disruption of signaling pathways such as those mediated by sonic hedgehog (Shh) or platelet-derived growth factor (Pdgf) causes craniofacial abnormalities, including cleft palate. The role that microRNAs play in modulating palatogenesis, however, is completely unknown. We show that, in zebrafish, the microRNA Mirn140 negatively regulates Pdgf signaling during palatal development, and we provide a mechanism for how disruption of Pdgf signaling causes palatal clefting.

mef2ca is required in cranial neural crest to effect Endothelin1 signaling in zebrafish.

Mef2 genes encode highly conserved transcription factors involved in somitic and cardiac mesoderm development in diverse bilaterians. Vertebrates have multiple mef2 genes. In mice, mef2c is required for heart and vascular development.

phospholipase C, beta 3 is required for Endothelin1 regulation of pharyngeal arch patterning in zebrafish.

Genetic and pharmacological studies demonstrate that Endothelin1 (Edn1) is a key signaling molecule for patterning the facial skeleton in fish, chicks, and mice. When Edn1 function is reduced early in development the ventral lower jaw and supporting structures are reduced in size and often fused to their dorsal upper jaw counterparts. We show that schmerle (she) encodes a zebrafish ortholog of Phospholipase C, beta 3 (Plcbeta3) required in cranial neural crest cells for Edn1 regulation of pharyngeal arch patterning.

Moz-dependent Hox expression controls segment-specific fate maps of skeletal precursors in the face.

Development of the facial skeleton depends on interactions between intrinsic factors in the skeletal precursors and extrinsic signals in the facial environment. Hox genes have been proposed to act cell-intrinsically in skeletogenic cranial neural crest cells (CNC) for skeletal pattern. However, Hox genes are also expressed in other facial tissues, such as the ectoderm and endoderm, suggesting that Hox genes could also regulate extrinsic signalling from non-CNC tissues.

Early Hedgehog signaling from neural to oral epithelium organizes anterior craniofacial development.

Hedgehog (Hh) signaling plays multiple roles in the development of the anterior craniofacial skeleton. We show that the earliest function of Hh is indirect, regulating development of the stomodeum, or oral ectoderm. A subset of post-migratory neural crest cells, that gives rise to the cartilages of the anterior neurocranium and the pterygoid process of the palatoquadrate in the upper jaw, condenses upon the upper or roof layer of the stomodeal ectoderm in the first pharyngeal arch.