Casz1 is required for both inner hair cell fate stabilization and outer hair cell survival.

Cochlear inner hair cells (IHCs) and outer hair cells (OHCs) require different transcription factors for their cell fate stabilization and survival, suggesting separate mechanisms are involved. Here, we found that the transcription factor Casz1 was crucial for early IHC fate consolidation and for OHC survival during mouse development. Loss of Casz1 resulted in transdifferentiation of IHCs into OHCs, without affecting OHC production.

Revisiting the Potency of Tbx2 Expression in Transforming Outer Hair Cells into Inner Hair Cells at Multiple Ages In Vivo.

The mouse auditory organ cochlea contains two types of sound receptors: inner hair cells (IHCs) and outer hair cells (OHCs). Tbx2 is expressed in IHCs but repressed in OHCs, and neonatal OHCs that misexpress Tbx2 transdifferentiate into IHC-like cells. However, the extent of this switch from OHCs to IHC-like cells and the underlying molecular mechanism remain poorly understood.

Fgf8: A New Genetic Mouse Model for Specifically Labeling and Sorting Cochlear Inner Hair Cells.

The cochlear auditory epithelium contains two types of sound receptors, inner hair cells (IHCs) and outer hair cells (OHCs). Mouse models for labelling juvenile and adult IHCs or OHCs exist; however, labelling for embryonic and perinatal IHCs or OHCs are lacking. Here, we generated a new knock-in Fgf8 (Fgf8) strain, in which the expression of a series of three GFP fragments is controlled by endogenous Fgf8 cis-regulatory elements.

Epistatic genetic interactions between Insm1 and Ikzf2 during cochlear outer hair cell development.

The cochlea harbors two types of sound receptors, outer hair cells (OHCs) and inner hair cells (IHCs). OHCs transdifferentiate into IHCs in Insm1 mutants, and OHCs in Ikzf2-deficient mice are dysfunctional and maintain partial IHC gene expression. Insm1 potentially acts as a positive but indirect regulator of Ikzf2, considering that Insm1 is expressed earlier than Ikzf2 and primarily functions as a transcriptional repressor.

Fully integrated on-line strategy for highly sensitive proteome profiling of 10-500 mammalian cells.

Recent development in proteomic sample preparation using nanofluidic devices has made single-cell proteome profiling possible. However, these nanofluidic devices require special expertise and costly nanopipetting instruments. They are also specially designed for single cells, are not well-suited for profiling rare samples consisting of a few hundred mammalian cells, arguably a more common need that remains a great challenge.

Three distinct enhancers cooperate for sound receptor hair cell development.

Cochlear hair cells (HCs) in the inner ear are responsible for sound detection. For HC fate specification, the master transcription factor Atoh1 is both necessary and sufficient. expression is dynamic and tightly regulated during development, but the -regulatory elements mediating this regulation remain unresolved.

Mosaic CRISPR-stop enables rapid phenotyping of nonsense mutations in essential genes.

CRISPR-stop converts protein-coding sequences into stop codons, which, in the appropriate location, results in a null allele. CRISPR-stop induction in one-cell-stage zygotes generates Founder 0 (F0) mice that are homozygous mutants; this avoids mouse breeding and serves as a rapid screening approach for nonlethal genes. However, loss of function of 25% of mammalian genes causes early lethality.

Fate-mapping analysis using Rorb-IRES-Cre reveals apical-to-basal gradient of Rorb expression in mouse cochlea.

Background: Conditional loss-of-function studies are widely conducted using the Cre/Loxp system because this helps circumvent embryonic or neonatal lethality problems. However, Cre strains specific to the inner ear are lacking, and thus lethality frequently occurs even in conditional knockout studies.

Results: Here, we report a Rorb-IRES-Cre knockin mouse strain in which the Cre recapitulates the expression pattern of endogenous Rorb (RAR-related orphan receptor beta).

A Critical Role of Presynaptic Cadherin/Catenin/p140Cap Complexes in Stabilizing Spines and Functional Synapses in the Neocortex.

The formation of functional synapses requires coordinated assembly of presynaptic transmitter release machinery and postsynaptic trafficking of functional receptors and scaffolds. Here, we demonstrate a critical role of presynaptic cadherin/catenin cell adhesion complexes in stabilizing functional synapses and spines in the developing neocortex. Importantly, presynaptic expression of stabilized β-catenin in either layer (L) 4 excitatory neurons or L2/3 pyramidal neurons significantly upregulated excitatory synaptic transmission and dendritic spine density in L2/3 pyramidal neurons, while its sparse postsynaptic expression in L2/3 neurons had no such effects.

Phosphatidylinositol 3,4-bisphosphate regulates neurite initiation and dendrite morphogenesis via actin aggregation.

Neurite initiation is critical for neuronal morphogenesis and early neural circuit development. Recent studies showed that local actin aggregation underneath the cell membrane determined the site of neurite initiation. An immediately arising question is what signaling mechanism initiated actin aggregation.

Coordinated Spine Pruning and Maturation Mediated by Inter-Spine Competition for Cadherin/Catenin Complexes.

Dendritic spines are postsynaptic compartments of excitatory synapses that undergo dynamic changes during development, including rapid spinogenesis in early postnatal life and significant pruning during adolescence. Spine pruning defects have been implicated in developmental neurological disorders such as autism, yet much remains to be uncovered regarding its molecular mechanism. Here, we show that spine pruning and maturation in the mouse somatosensory cortex are coordinated via the cadherin/catenin cell adhesion complex and bidrectionally regulated by sensory experience.

A novel Wnt5a-Frizzled4 signaling pathway mediates activity-independent dendrite morphogenesis via the distal PDZ motif of Frizzled 4.

The morphology of the dendritic tree is critical to neuronal function and neural circuit wiring. Several Wnt family members have been demonstrated to play important roles in dendrite development. However, the Wnt receptors responsible for mediating this process remain largely elusive.