Spatio-temporal development of astrocytes heterogeneity in the spinal cord

SISTER, CATERINA LAURA; LANUZA, GUILLERMO

Valparaiso

Congreso; Latin American Developmental Biology Conference; 2024

EMBO

Astrocytes are the most numerous cell type in the mammalian central nervous system. They are involved in the maintenance and regulation of neurological functions, and their impairment results in the initiation or progression of several pathologies. In opposition to the advances in elucidating the basic principles of neuronal subtype specification, much less is known about the influence of developmental origin on astrocytic diversity. Here we show that distinct dorso-ventral progenitor domains of the mouse neural tube (identified by Nkx6.1, Pax3/6/7, Dbx1, Ascl1) produce astrocyte subsets that populate precise regions of the spinal cord. Each population displays internal heterogeneity with grey matter protoplasmic, and white matter fibrous and subpial astrocytes.We fate mapped individual progenitor cells to assess whether grey and white matter cells originate from same or distinct ventricular zone precursors. GlastCreER mice were used in combination with td-tomato reports or the mosaic analysis with double markers clonal system (MADM), which allow the analysis of the morphology and location of related cells. These experiments showed that each progenitor tends to produce either protoplasmic or fibrous/subpial astrocytes. White matter clones are composed by 1-4 descendants, while grey matter astrocytes seem to differentiate directly from ventricular progenitors without division in the mantle zone. In addition, these experiments show differences in the timing of astrocyte subtypes development in distinct regions of the spinalcord. In conclusion, these results unravel aspects of astrocyte heterogeneity. Protoplasmic or fibrous astrocytes seem to originate from distinct lineages and their positional identity is a key factor in creating astrocyte diversity.