MOSAIC ATOH1 DELETION IN THE CHICK AUDITORY EPITHELIUM REVEALS A HOMEOSTATIC MECHANISM TO RESTORE HAIR CELL NUMBER.

The mechanosensory hair cell of the vertebrate inner ear responds to the mechanical deflections that result from hearing or change in the acceleration due to gravity, to allow us to perceive and interpret sounds, maintain balance and spatial orientation. In mammals, ototoxic compounds, disease, and acoustic trauma can result in damage and extrusion of hair cells, without replacement, resulting in hearing loss. In contrast, non-mammalian vertebrates can regenerate sensory hair cells. Upon damage, hair cells are extruded and an associated cell type, the supporting cell is transformed into a hair cell. The mechanisms that can trigger regeneration are not known. Using mosaic deletion of the hair cell master gene, Atoh1, in the embryonic avian inner ear, we find that despite hair cells depletion at E9, by E12, hair cell number is restored in sensory epithelium. Our study suggests a homeostatic mechanism can restores hair cell number in the basilar papilla, that is activated when juxtracrine signalling is disrupted. Restoration of hair cell numbers during development may mirror regenerative processes, and our work provides insights into the mechanisms that trigger regeneration.

A Comprehensive Review on Nanomedicine: Promising Approach for Treatment of Brain Tumor through Intranasal Administration.

Brain tumors have become one of the deadliest cancers; however, their treatment is still limited by conventional approaches. Brain tumors, among other CNS diseases, are the most lethal form of cancer due to ineffective diagnosis and profiling. The major limiting factor in treating brain tumors is the blood-brain barrier (BBB), and the required therapeutic concentration is not achieved. Hence, most drugs are prescribed at higher doses, which have several unwanted side effects. Nanotechnology has emerged as an interesting and promising new approach for treating neurological disorders, including brain tumors, with the potential to overcome concerns related to traditional therapeutic approaches. Moreover, biomimetic nanomaterials have been introduced to successfully cross the blood-brain barrier and be consumed by deep skin cancer for imaging brain tumors using multimodal functional nanostructures for more specific and reliable medical assessment. These nanomedicines can address several challenges by enhancing the bioavailability of therapeutics through controlled pharmacokinetics and pharmacodynamics. Further nasal drug delivery has been considered as an alternative approach for the brain's targeting for the treatment of several CNS diseases. A drug can be directly delivered to the brain by bypassing the BBB through intranasal administration. This review discusses intranasal nanomedicine-based therapies for brain tumor targeting, which can be explored from different perspectives.

In Ovo and Ex Ovo Methods to Study Avian Inner Ear Development.

The inner ear perceives sound and maintains balance using the cochlea and vestibule. It does this by using a dedicated mechanosensory cell type known as the hair cell. Basic research in the inner ear has led to a deep understanding of how the hair cell functions, and how dysregulation can lead to hearing loss and vertigo. For this research, the mouse has been the pre-eminent model system. However, mice, like all mammals, have lost the ability to replace hair cells. Thus, when trying to understand cellular therapies for restoring inner ear function, complementary studies in other vertebrate species could provide further insights. The auditory epithelium of birds, the basilar papilla (BP), is a sheet of epithelium composed of mechanosensory hair cells (HCs) intercalated by supporting cells (SCs). Although the anatomical architecture of the basilar papilla and the mammalian cochlea differ, the molecular mechanisms of inner ear development and hearing are similar. This makes the basilar papilla a useful system for not only comparative studies but also to understand regeneration. Here, we describe dissection and manipulation techniques for the chicken inner ear. The technique shows genetic and small molecule inhibition methods, which offer a potent tool for studying the molecular mechanisms of inner ear development. In this paper, we discuss in ovo electroporation techniques to genetically perturb the basilar papilla using CRIPSR-Cas9 deletions, followed by dissection of the basilar papilla. We also demonstrate the BP organ culture and optimal use of culture matrices, to observe the development of the epithelium and the hair cells.