A C-terminal motif containing a PKC phosphorylation site regulates γ-Protocadherin-mediated dendrite arborization in the cerebral cortex in vivo.

The Pcdhg gene cluster encodes 22 γ-Protocadherin (γ-Pcdh) cell adhesion molecules that critically regulate multiple aspects of neural development, including neuronal survival, dendritic and axonal arborization, and synapse formation and maturation. Each γ-Pcdh isoform has unique protein domains-a homophilically interacting extracellular domain and a juxtamembrane cytoplasmic domain-as well as a C-terminal cytoplasmic domain shared by all isoforms. The extent to which isoform-specific versus shared domains regulate distinct γ-Pcdh functions remains incompletely understood.

A C-terminal motif containing a PKC phosphorylation site regulates γ-Protocadherin-mediated dendrite arborization in the cerebral cortex .

The gene cluster encodes 22 γ-Protocadherin (γ-Pcdh) cell adhesion molecules that critically regulate multiple aspects of neural development, including neuronal survival, dendritic and axonal arborization, and synapse formation and maturation. Each γ-Pcdh isoform has unique protein domains-a homophilically-interacting extracellular domain and a juxtamembrane cytoplasmic domain-as well as a C-terminal cytoplasmic domain shared by all isoforms. The extent to which isoform-specific shared domains regulate distinct γ-Pcdh functions remains incompletely understood.

γ-Protocadherins control synapse formation and peripheral branching of touch sensory neurons.

Light touch sensation begins with activation of low-threshold mechanoreceptor (LTMR) endings in the skin and propagation of their signals to the spinal cord and brainstem. We found that the clustered protocadherin gamma (Pcdhg) gene locus, which encodes 22 cell-surface homophilic binding proteins, is required in somatosensory neurons for normal behavioral reactivity to a range of tactile stimuli. Developmentally, distinct Pcdhg isoforms mediate LTMR synapse formation through neuron-neuron interactions and peripheral axonal branching through neuron-glia interactions.

Serotonin signaling by maternal neurons upon stress ensures progeny survival.

Germ cells are vulnerable to stress. Therefore, how organisms protect their future progeny from damage in a fluctuating environment is a fundamental question in biology. We show that in , serotonin released by maternal neurons during stress ensures the viability and stress resilience of future offspring.

CRISPR/Cas9 interrogation of the mouse Pcdhg gene cluster reveals a crucial isoform-specific role for Pcdhgc4.

The mammalian Pcdhg gene cluster encodes a family of 22 cell adhesion molecules, the gamma-Protocadherins (γ-Pcdhs), critical for neuronal survival and neural circuit formation. The extent to which isoform diversity-a γ-Pcdh hallmark-is required for their functions remains unclear. We used a CRISPR/Cas9 approach to reduce isoform diversity, targeting each Pcdhg variable exon with pooled sgRNAs to generate an allelic series of 26 mouse lines with 1 to 21 isoforms disrupted via discrete indels at guide sites and/or larger deletions/rearrangements.

A critical role for the nuclear protein Akirin2 in the formation of mammalian muscle in vivo.

Evolutionarily conserved Akirin nuclear proteins interact with chromatin remodeling complexes at gene enhancers and promoters, and have been reported to regulate cell proliferation and differentiation. Of the two mouse Akirin genes, Akirin2 is essential during embryonic development, with known in vivo roles in immune system function and the formation of the cerebral cortex. Here we demonstrate that Akirin2 is critical for mouse myogenesis, a tightly regulated developmental process through which myoblast precursors fuse to form mature skeletal muscle fibers.

An essential role for the nuclear protein Akirin2 in mouse limb interdigital tissue regression.

The regulation of interdigital tissue regression requires the interplay of multiple spatiotemporally-controlled morphogen gradients to ensure proper limb formation and release of individual digits. Disruption to this process can lead to a number of limb abnormalities, including syndactyly. Akirins are highly conserved nuclear proteins that are known to interact with chromatin remodelling machinery at gene enhancers.

Akirin2 is essential for the formation of the cerebral cortex.

Background: The proper spatial and temporal regulation of dorsal telencephalic progenitor behavior is a prerequisite for the formation of the highly-organized, six-layered cerebral cortex. Premature differentiation of cells, disruption of cell cycle timing, excessive apoptosis, and/or incorrect neuronal migration signals can have devastating effects, resulting in a number of neurodevelopmental disorders involving microcephaly and/or lissencephaly. Though genes encoding many key players in cortical development have been identified, our understanding remains incomplete.

Neural crest cell motility in valproic acid.

Neural crest cells (NCCs) exit the dorsal neural tube and migrate to sites where they form diverse tissues. Valproic acid (VPA) is an anticonvulsant drug that induces neural tube and related defects. Altered NCC migration and proliferation have been proposed as mechanisms of teratogenicity.