Developmental dynamics of PAFAH1B subunits during mouse brain development

Abstract

Platelet-activating factor (PAF) mediates an array of biological processes in the mammalian central nervous system as a bioactive lipid messenger in synaptic function and dysfunction (plasticity, memory, and neurodegeneration). The intracellular enzyme that deacetylates the PAF (PAFAH1B) is composed of a tetramer of two catalytic subunits, ALPHA1 (PAFAH1B3) and ALPHA2 (PAFAH1B2), and a regulatory dimer of LIS1 (PAFAH1B1). We have investigated the mouse PAFAH1B subunit genes during brain development in normal mice and in mice with a hypomorphic allele for Lis1 (Lis1/sLis1; Cahana et al. [2001] Proc Natl Acad Sci U S A 98:6429-6434). We have analyzed quantitatively (by means of real-time polymerase chain reaction) and qualitatively (by in situ hybridization techniques) the amounts and expression patterns of their transcription in developing and postnatal brain, focusing mainly on differences in two laminated encephalic regions, the forebrain (telencephalon) and hindbrain (cerebellum) separately. The results revealed significant differences in cDNA content between these two brain subdivisions but, more importantly, between the LIS1 complex subunits. In addition, we found significant spatial differences in gene expression patterns. Comparison of results obtained with Lis1/sLis1 analysis also revealed significant temporal and spatial differences in Alpha1 and Lis1 expression levels. Thus, small changes in the amount of the Lis1 gene may differentially regulate expression of Alpha1 and Alpha2, depending on the brain region, which suggests different roles for each LIS1 complex subunit during neural differentiation and neural migration.

Transcription factor expression defines subclasses of developing projection neurons highly similar to single-cell RNA-seq subtypes

“…Each cluster contained bona fide lamination markers (SI Appendix, Table S1), including the UL TFs Nfix and Cux1 in the UL cluster, the DL TFs Sox5 and Tle4 in the DL cluster, the DL CPN marker Ptn in the UL-like cluster (36), and the DL-enriched Lmo3 in the DL-subset cluster (37). The three genes that encode subunits of the plateletactivating factor acetylhydrolase 1B complex (PAFAH1B2), an enzyme involved in neuron migration and synaptic function, were also differentially expressed: Pafah1b1 (Lis1) and Pafah1b2 clustered with DL transcripts, and Pafah1b3 clustered with UL transcripts, consistent with a previous report (38).…”

Differential chromatin accessibility in developing projection neurons is correlated with transcriptional regulation of cell fate

“…Pafah1b1 (Lis1) and Pafah1b2 clustered with DL transcripts, and Pafah1b3 clustered with UL transcripts, consistent with a previous report showing different expression patterns of these subunits 33 . Moreover, when we limited hierarchical clustering to only those transcripts that encode TFs, UL and DL subclasses clearly segregated (Fig.…”

Distinct disruptions in Land's cycle remodeling of glycerophosphocholines in murine cortex mark symptomatic onset and progression in two Alzheimer's disease mouse models

“…The PAFAH1b trimer is composed of two catalytic subunits, α 1 and/ or α 2 , and one regulatory subunit, LIS1 and is expressed by neurons not glia in brain (Escamez et al . ). α 2 and LIS1 protein levels did not change with age in Tg and Non‐Tg littermates (Fig.…”