A thermodynamic perspective on mammalian neural crest ingression.

The ingression of neural crest cells from an ectodermal to a mesodermal layer is regulated by instructive, directional cues and potentially stochastic, biophysical parameters such as differential cell adhesion and tension heterogeneity. However, a cohesive framework in which to consider how various influences contribute to ingression remains elusive. Here, we observe the cell behaviors of the murine neural crest in three dimensions over time and apply a free energy framework to more wholly understand why cells ingress.

Tissue stiffness mapping by light sheet elastography.

Tissue stiffness plays a crucial role in regulating morphogenesis. The ability to measure and monitor the dynamic progression of tissue stiffness is important for generating and testing mechanistic hypotheses. Methods to measure tissue properties in vivo have been emerging but present challenges with spatial and temporal resolution especially in 3D, by their reliance on highly specialized equipment, and/or due to their invasive nature.

Local Control for Pediatric Rhabdomyosarcoma of the Extremities: Is Radiotherapy Always Required After Adequate Surgical Resection? A CanSaRCC Study.

Objectives: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and young adults. Typically, treatment involves a multimodal approach, with radiotherapy (RT) being a standard choice alongside surgical resection for local control, particularly in cases harboring fusions involving FOXO1. However, the long-term consequences of offering RT especially to the extremity in children can be significant including growth delay, contracture, arthritis, and secondary malignancy.

A fibronectin gradient remodels mixed-phase mesoderm.

Physical processes ultimately shape tissue during development. Two emerging proposals are that cells migrate toward stiffer tissue (durotaxis) and that the extent of cell rearrangements reflects tissue phase, but it is unclear whether and how these concepts are related. Here, we identify fibronectin-dependent tissue stiffness as a control variable that underlies and unifies these phenomena in vivo.

Mesenchymal Wnts are required for morphogenetic movements of calvarial osteoblasts during apical expansion.

Apical expansion of calvarial osteoblast progenitors from the cranial mesenchyme (CM) above the eye is integral to calvarial growth and enclosure of the brain. The cellular behaviors and signals underlying the morphogenetic process of calvarial expansion are unknown. Time-lapse light-sheet imaging of mouse embryos revealed calvarial progenitors intercalate in 3D in the CM above the eye, and exhibit protrusive and crawling activity more apically.

Apical expansion of calvarial osteoblasts and suture patency is dependent on fibronectin cues.

The skull roof, or calvaria, is comprised of interlocking plates of bones that encase the brain. Separating these bones are fibrous sutures that permit growth. Currently, we do not understand the instructions for directional growth of the calvaria, a process which is error-prone and can lead to skeletal deficiencies or premature suture fusion (craniosynostosis, CS).

Mesenchymal Wnts are required for morphogenetic movements of calvarial osteoblasts during apical expansion.

Apical expansion of calvarial osteoblast progenitors from the cranial mesenchyme (CM) above the eye is integral for calvarial growth and enclosure of the brain. The cellular behaviors and signals underlying the morphogenetic process of calvarial expansion are unknown. During apical expansion, we found that mouse calvarial primordia have consistent cellular proliferation, density, and survival with complex tissue scale deformations, raising the possibility that morphogenetic movements underlie expansion.

Shape-driven confluent rigidity transition in curved biological tissues.

Collective cell motions underlie structure formation during embryonic development. Tissues exhibit emergent multicellular characteristics such as jamming, rigidity transitions, and glassy dynamics, but there remain questions about how those tissue-scale dynamics derive from local cell-level properties. Specifically, there has been little consideration of the interplay between local tissue geometry and cellular properties influencing larger-scale tissue behaviors.

Primitive Myxoid Mesenchymal Tumor of Infancy With Brain Metastasis Case Report and Literature Review.

Primitive myxoid mesenchymal tumor of infancy (PMMTI), a rare soft tissue tumor with distinct characteristics. PMMTI tends to have an aggressive local course, with multiple relapses and poor response to treatment. Rare cases of distant metastases have been described before.

Management of Brachial Plexus Birth Injury: The SickKids Experience.

This article describes the approach utilized by the multidisciplinary team at Sick Kids Hospital to evaluate and treat patients with brachial plexus birth injury (BPBI). This approach has been informed by more than 30 years of experience treating over 1,800 patients with BPBI and continues to evolve over time. The objective of this article is to provide readers with a practical overview of the Sick Kids approach to the management of infants with BPBI.

Surgery for internal rotation contracture in infancy may obviate the need for brachial plexus nerve reconstruction: early experience.

Background: Shoulder internal rotation contracture and subluxation in the first year of life has long been recognized in some patients with brachial plexus birth injury (BPBI). Surgical management of shoulder pathology has traditionally been undertaken following nerve reconstruction as necessary. In some patients; however, shoulder pathology may impair or obscure functional neuromuscular recovery of the upper extremity.

Recent Advances in the Treatment of Brachial Plexus Birth Injury.

Learning Objectives: After studying this article, the participant should be able to: 1. Describe methods of clinical evaluation for neurologic recovery in brachial plexus birth injury. 2.

Rotationplasty with Tibial Nerve Coaptation: A Case Report.

Case: We present the case of a 14-year-old adolescent boy with a distal femoral osteosarcoma partially encasing the tibial nerve. He underwent rotationplasty with resection and coaptation (end-to-end repair) of the tibial nerve. By 1 year postoperatively, he had recovered sensation on the plantar aspect of his foot and Medical Research Council scale 4+/5 gastro-soleus contraction that powered extension of the new knee.

Apical expansion of calvarial osteoblasts and suture patency is dependent on graded fibronectin cues.

The skull roof, or calvaria, is comprised of interlocking plates of bone. Premature suture fusion (craniosynostosis, CS) or persistent fontanelles are common defects in calvarial development. Although some of the genetic causes of these disorders are known, we lack an understanding of the instructions directing the growth and migration of progenitors of these bones, which may affect the suture patency.

Transgenic force sensors and software to measure force transmission across the mammalian nuclear envelope in vivo.

Nuclear mechanotransduction is a growing field with exciting implications for the regulation of gene expression and cellular function. Mechanical signals may be transduced to the nuclear interior biochemically or physically through connections between the cell surface and chromatin. To define mechanical stresses upon the nucleus in physiological settings, we generated transgenic mouse strains that harbour FRET-based tension sensors or control constructs in the outer and inner aspects of the nuclear envelope.

patterns an accelerator-brake mechanical feedback through latent TGFβ to rotate the gut.

The vertebrate intestine forms by asymmetric gut rotation and elongation, and errors cause lethal obstructions in human infants. Rotation begins with tissue deformation of the dorsal mesentery, which is dependent on left-sided expression of the Paired-like transcription factor . The conserved morphogen induces asymmetric to govern embryonic laterality, but organ-level regulation of during gut asymmetry remains unknown.

Patterning the embryonic pulmonary mesenchyme.

Smooth muscle guides the morphogenesis of several epithelia during organogenesis, including the mammalian airways. However, it remains unclear how airway smooth muscle differentiation is spatiotemporally patterned and whether it originates from transcriptionally distinct mesenchymal progenitors. Using single-cell RNA-sequencing of embryonic mouse lungs, we show that the pulmonary mesenchyme contains a continuum of cell identities, but no transcriptionally distinct progenitors.

Bone Health in Osteosarcoma at Presentation and Its Impact on Cancer Treatment: A Case Series of 3 Pediatric Patients.

Osteosarcoma is the most common pediatric malignant bone tumor. Concomitant osteoporosis has typically been attributed to oncologic therapy. The present case series is aimed to describe 3 patients who presented with osteoporosis or osteopenia before, or early in, their oncology treatment.

Live imaging YAP signalling in mouse embryo development.

YAP protein is a critical regulator of mammalian embryonic development. By generating a near-infrared fusion YAP reporter mouse line, we have achieved high-resolution live imaging of YAP localization during mouse embryonic development. We have validated the reporter by demonstrating its predicted responses to blocking LATS kinase activity or blocking cell polarity.

Reconstruction for bone tumours of the shoulder and humerus in children and adolescents.

Reconstructions for paediatric bone tumours of the shoulder girdle and humerus are intended to optimize placement of the hand in space. Given the longevity of paediatric survivors of sarcoma, durability is an important planning consideration. Here, I review a subset of approaches based on anatomical site with an emphasis on function and longevity.

Non-rhabdomyosarcoma soft tissue sarcomas diagnosed in patients at a young age. An overview of clinical, pathological, and molecular findings.

Objective: Disease spectrum in pediatric sarcoma differs substantially from adults. We report a cohort of very young children with non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) detailing their molecular features, treatment, and outcome.

Methods: We report features of consecutive children (age <2 years) with NRSTS (2000-2017).

Radiological Assessment and Outcome of Local Disease Progression after Neoadjuvant Chemotherapy in Children and Adolescents with Localized Osteosarcoma.

Objective: We examined the interobserver reliability of local progressive disease (L-PD) determination using two major radiological response evaluation criteria systems (Response evaluation Criteria in Solid Tumors (RECIST) and the European and American Osteosarcoma Study (EURAMOS)) in patients diagnosed with localized osteosarcoma (OS). Additionally, we describe the outcomes of patients determined to experience L-PD.

Materials And Methods: Forty-seven patients diagnosed with localized OS between 2000 and 2012 at our institution were identified.

IRX3/5 regulate mitotic chromatid segregation and limb bud shape.

Pattern formation is influenced by transcriptional regulation as well as by morphogenetic mechanisms that shape organ primordia, although factors that link these processes remain under-appreciated. Here we show that, apart from their established transcriptional roles in pattern formation, IRX3/5 help to shape the limb bud primordium by promoting the separation and intercalation of dividing mesodermal cells. Surprisingly, IRX3/5 are required for appropriate cell cycle progression and chromatid segregation during mitosis, possibly in a nontranscriptional manner.

Magnetic Micromanipulation for Measurement of Stiffness Heterogeneity and Anisotropy in the Mouse Mandibular Arch.

The mechanical properties of tissues are pivotal for morphogenesis and disease progression. Recent approaches have enabled measurements of the spatial distributions of viscoelastic properties among embryonic and pathological model systems and facilitated the generation of important hypotheses such as durotaxis and tissue-scale phase transition. There likely are many unexpected aspects of embryo biomechanics we have yet to discover which will change our views of mechanisms that govern development and disease.