Biology subjects

Kozulin, P.

Publications and source records attributed to Kozulin, P..

2 recordsLinked to original sources

bioRxiv2022

LINE-1 retrotransposon activation intrinsic to interneuron development

Retrotransposons are a reservoir of cis-regulatory innovation1-3. Developmental programs that activate these elements could, in principle, manifest in lineage-specific retrotransposition. Somatic LINE-1 (L1) retrotransposon insertions have been detected in human and non-human primate neurons4-7. It is however unknown whether L1 is mobile in only some neuronal lineages, or therein regulates neurodevelopmental genes. Here, we report programmed L1 activation by SOX6, a transcription factor critical for parvalbumin (PV) interneuron development8-10. PV+ neurons permit L1 mobilization in vitro and in vivo, harbor unmethylated L1 promoters, and express full-length L1 mRNAs and proteins. Via nanopore long-read sequencing, we identify unmethylated L1 promoters proximal to PV+ neuron genes. One such L1, which promotes transcription of a novel CAPS2 gene isoform, significantly enhances neuron morphological complexity when phenotyped in vitro. These data highlight the contribution made by L1 cis-regulatory elements to PV+ neuron development and transcriptome diversity, uncovered due to L1 mobility in this milieu.

genomics↗

bioRxiv2020

The DCC receptor regulates astroglial development essential for telencephalic morphogenesis and corpus callosum formation

The forebrain hemispheres are predominantly separated during embryogenesis by the interhemispheric fissure (IHF). Radial astroglia remodel the IHF to form a continuous substrate between the hemispheres for midline crossing of the corpus callosum (CC) and hippocampal commissure (HC). DCC and NTN1 are molecules that have an evolutionarily conserved function in commissural axon guidance. The CC and HC are absent in Dcc and Ntn1 knockout mice, while other commissures are only partially affected, suggesting an additional aetiology in forebrain commissure formation. Here, we find that these molecules play a critical role in regulating astroglial development and IHF remodelling during CC and HC formation. Human subjects with DCC mutations display disrupted IHF remodelling associated with CC and HC malformations. Thus, axon guidance molecules such as DCC and NTN1 first regulate the formation of a midline substrate for dorsal commissures prior to their role in regulating axonal growth and guidance across it.

neuroscience↗