The primary cilia: Orchestrating cranial neural crest cell development.

Primary cilia (hereafter "cilia") are microtubule-based antenna-like organelles projecting from the surface of vertebrate cells. Cilia can serve as cellular antennae controlling cell growth and differentiation. Absent or dysfunctional cilia frequently lead to craniofacial anomalies known as craniofacial ciliopathies.

Ciliary and non-ciliary functions of Rab34 during craniofacial bone development.

The primary cilium is a hair-like projection that controls cell development and tissue homeostasis. Although accumulated studies identify the molecular link between cilia and cilia-related diseases, the underlying etiology of ciliopathies has not been fully understood. In this paper, we determine the function of Rab34, a small GTPase, as a key regulator for controlling ciliogenesis and type I collagen trafficking in craniofacial development.

GSK3 and lamellipodin balance lamellipodial protrusions and focal adhesion maturation in mouse neural crest migration.

Neural crest cells are multipotent cells that delaminate from the neuroepithelium, migrating throughout the embryo. Aberrant migration causes developmental defects. Animal models are improving our understanding of neural crest anomalies, but in vivo migration behaviors are poorly understood.

Identification of distinct subpopulations of Gli1-lineage cells in the mouse mandible.

The Hedgehog pathway gene Gli1 has been proposed to mark a subpopulation of skeletal stem cells (SSCs) in craniofacial bone. Skeletal stem cells (SSCs) are multi-potent cells crucial for the development and homeostasis of bone. Recent studies on long bones have suggested that skeletal stem cells in endochondral or intramembranous ossification sites have different differentiation capacities.

Local depletion of proteoglycans mediates cartilage tissue repair in an ex vivo integration model.

Successfully replacing damaged cartilage with tissue-engineered constructs requires integration with the host tissue and could benefit from leveraging the native tissue's intrinsic healing capacity; however, efforts are limited by a poor understanding of how cartilage repairs minor defects. Here, we investigated the conditions that foster natural cartilage tissue repair to identify strategies that might be exploited to enhance the integration of engineered/grafted cartilage with host tissue. We damaged porcine articular cartilage explants and using a combination of pulsed SILAC-based proteomics, ultrastructural imaging, and catabolic enzyme blocking strategies reveal that integration of damaged cartilage surfaces is not driven by neo-matrix synthesis, but rather local depletion of proteoglycans.

Identification of a novel variant of the ciliopathic gene FUZZY associated with craniosynostosis.

Craniosynostosis is a birth defect occurring in approximately one in 2000 live births, where premature fusion of the cranial bones inhibits growth of the skull during critical periods of brain development. The resulting changes in skull shape can lead to compression of the brain, causing severe complications. While we have some understanding of the molecular pathology of craniosynostosis, a large proportion of cases are of unknown genetic aetiology.

Anaplastic lymphoma kinase (alk), a neuroblastoma associated gene, is expressed in neural crest domains during embryonic development of Xenopus.

Neuroblastoma is a neural crest-derived paediatric cancer that is the most common and deadly solid extracranial tumour of childhood. It arises when neural crest cells fail to follow their differentiation program to give rise to cells of the sympathoadrenal lineage. These undifferentiated cells can proliferate and migrate, forming tumours mostly found associated with the adrenal glands.

Induction of Neural Crest Stem Cells From Bardet-Biedl Syndrome Patient Derived hiPSCs.

Neural crest cells arise in the embryo from the neural plate border and migrate throughout the body, giving rise to many different tissue types such as bones and cartilage of the face, smooth muscles, neurons, and melanocytes. While studied extensively in animal models, neural crest development and disease have been poorly described in humans due to the challenges in accessing embryonic tissues. In recent years, patient-derived human induced pluripotent stem cells (hiPSCs) have become easier to generate, and several streamlined protocols have enabled robust differentiation of hiPSCs to the neural crest lineage.

A quantitative approach for determining the role of geometrical constraints when shaping mesenchymal condensations.

In embryogenesis, mesenchymal condensation is a critical event during the formation of many organ systems, including cartilage and bone. During organ formation, mesenchymal cells aggregate and undergo compaction while activating developmental programmes. The final three-dimensional form of the organ, as well as cell fates, can be influenced by the size and shape of the forming condensation.

Micrognathia in mouse models of ciliopathies.

Defects in the development of the mandible can lead to micrognathia, or small jaw, which manifests in ciliopathic conditions, such as orofaciodigital syndrome, Meckel-Gruber syndrome, and Bardet-Biedl syndrome. Although micrognathia occurs frequently in human and mouse ciliopathies, it has been difficult to pinpoint the underlying cellular causes. In this mini-review, we shed light on the tissue-specific contributions to ciliary dysfunction in the development of the mandible.

Fuz mutant mice reveal shared mechanisms between ciliopathies and FGF-related syndromes.

Ciliopathies are a broad class of human disorders with craniofacial dysmorphology as a common feature. Among these is high arched palate, a condition that affects speech and quality of life. Using the ciliopathic Fuz mutant mouse, we find that high arched palate does not, as commonly suggested, arise from midface hypoplasia.

Novel reporter alleles of GSK-3α and GSK-3β.

Glycogen Synthase Kinase 3 (GSK-3) is a key player in development, physiology and disease. Because of this, GSK-3 inhibitors are increasingly being explored for a variety of applications. In addition most analyses focus on GSK-3β and overlook the closely related protein GSK-3α.