The thalamus, a crucial regulator of cortical functions, is composed of many nuclei arranged in a spatially complex pattern. Thalamic neurogenesis occurs over a short period during mammalian embryonic development. These features have hampered the effort to understand how regionalization, cell divisions, and fate specification are coordinated and produce a wide array of nuclei that exhibit distinct patterns of gene expression and functions. Here, we performed in vivo clonal analysis to track the divisions of individual progenitor cells and spatial allocation of their progeny in the developing mouse thalamus. Quantitative analysis of clone compositions revealed evidence for sequential generation of distinct sets of thalamic nuclei based on the location of the founder progenitor cells. Furthermore, we identified intermediate progenitor cells that produced neurons populating more than one thalamic nuclei, indicating a prolonged specification of nuclear fate. Our study reveals an organizational principle that governs the spatial and temporal progression of cell divisions and fate specification and provides a framework for studying cellular heterogeneity and connectivity in the mammalian thalamus.

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The thalamus, a crucial regulator of cortical functions, is composed of many nuclei arranged in a spatially complex pattern. Thalamic neurogenesis occurs over a short period during embryonic development. These features have hampered the effort to understand how regionalization, cell divisions and fate specification are coordinated and produce a wide array of nuclei that exhibit distinct patterns of gene expression and functions. Here, we performed an in vivo clonal analysis to track the divisions of individual progenitor cells and spatial allocation of their progeny in the developing thalamus. Quantitative analysis of clone compositions revealed evidence for sequential generation of distinct sets of thalamic nuclei that are associated with the location of the founder cell. Furthermore, we identified intermediate progenitor cells that produced two to four neurons populating more than one thalamic nuclei, indicating a late specification of nuclear fate. Our study reveals an organizational principle that governs the spatial and temporal progression of cell divisions and fate specification, and provides a framework for studying cellular heterogeneity and connectivity in the thalamus.

Microglia play many critical roles in neural development. Recent single-cell RNAsequencing studies have found diversity of microglia both across different stages and within the same stage in the developing brain. However, how such diversity is controlled during development is poorly understood. In this study, we first found the expression of the macrophage mannose receptor CD206 in early-stage embryonic microglia on mouse brain sections. This expression showed a sharp decline between E12.5 and E13.5 across the central nervous system. We next tested the roles of the microglia-expressed zinc finger transcription factor SALL1 in this early transition of gene expression. By deleting Sall1 specifically in microglia, we found that many microglia continued to express CD206 when it is normally downregulated. In addition, the mutant microglia continued to show less ramified morphology in comparison with controls even into postnatal stages. Thus, SALL1 is required for early microglia to transition into a more mature status during development.