Biomedical subjects

Luc Mathis

Publications and source records attributed to Luc Mathis.

4 recordsLinked to original sources

PubMed2006

Clonal origin of the mammalian forebrain from widespread oriented mixing of early regionalized neuroepithelium precursors.

The forebrain is formed by remodeling and growth of the anterior neural plate. This morphogenesis occurs in response to inductive signals during gastrulation and neurulation but is poorly understood at the cellular level. Here, we have used the LaacZ method of single cells labeling to visualize, at E12.5, clones originated at early stages of mouse forebrain development. The largest clones show that single progenitors can give rise to neuroepithelial cells dispersed across the forebrain. A significant fraction of the clones, and even relatively small ones, populated both the diencephalon and the telencephalon, indicating that the clonal separation between diencephalic and telencephalic progenitors is transient and/or partial. However, two groups of large clones, populating either the diencephalon or the telencephalon, dispersed within their respective domains, suggesting an early regionalization between some diencephalic and telencephalic progenitors. Widespread oriented mixing within these territories and then clonal expansion into smaller domains probably follow this initial regionalization. These data are consistent with a model of progressive specification of forebrain domains. We propose that the ordered expansion of early regionalized progenitor pools for the diencephalon and telencephalon could establish a potential link between early inductive signals and forebrain morphogenesis.

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PubMed2003

Progressive restriction of cell fates in relation to neuroepithelial cell mingling in the mouse cerebellum.

Neurogenesis in the cerebellum proceeds through a temporal series of cell production from two separate epithelia, the ventricular zone (VZ) and the external granule cell layer (EGL). Using the laacZ cell lineage tracer in transgenic mice, we describe cellular clones whose dates of birth span the entire period of cerebellar development and deduce a sequence of cell dispersion leading to the final allocation of cells in the cerebellum. Clones probably labeled early during neural tube formation show that individual progenitors can give rise to all cerebellar cell types. The distribution of clonally related granule cells in these clones indicates a mediolateral organization of EGL progenitors already established before the allocation of the EGL progenitors to the cerebellum. Clones restricted to the cerebellar VZ show that the VZ derives progenitors for deep nuclei and multipotent cortical progenitors, which lose their systematic lineage relationship when longitudinal cell intermingling in the cerebellar VZ becomes more limited. The small clones also show that cell dispersion is radial in the internal granule layer and tangential in the molecular layer. Together, the data demonstrate the broad maintenance of the relative order of cells from neural tube stages to the adult cerebellum.

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PubMed2003

Msx1 is required for dorsal diencephalon patterning.

The dorsal midline of the neural tube has recently emerged as a major signaling center for dorsoventral patterning. Msx genes are expressed at the dorsal midline, although their function at this site remains unknown. Using Msx1(nlacZ) mutant mice, we show that the normal expression domain of Msx1 is interrupted in the pretectum of mutant embryos. Morphological and gene expression data further indicate that a functional midline is not maintained along the whole prosomere 1 in Msx1 mutant mice. This results in the downregulation of genes expressed laterally to the midline in prosomere 1, confirming the importance of the midline as a signaling center. Wnt1 is essential for dorsoventral patterning of the neural tube. In the Msx1 mutant, Wnt1 is downregulated before the midline disappears, suggesting that its expression depends on Msx1. Furthermore, electroporation in the chick embryo demonstrates that Msx1 can induce Wnt1 expression in the diencephalon neuroepithelium and in the lateral ectoderm. In double Msx1/Msx2 mutants, Wnt1 expression is completely abolished at the dorsal midline of the diencephalon and rostral mesencephalon. This indicates that Msx genes may regulate Wnt1 expression at the dorsal midline of the neural tube. Based on these results, we propose a model in which Msx genes are intermediary between Bmp and Wnt at this site.

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PubMed2002

Cellular patterning of the vertebrate embryo.

Recent studies show that cell dispersal is a widespread phenomenon in the development of early vertebrate embryos. These cell movements coincide with major decisions for the spatial organization of the embryo, and they parallel genetic patterning events. For example, in the central nervous system, cell dispersal is first mainly anterior-posterior and subsequently dorsal-ventral. Thus, genes expressed in signaling centers of the embryo probably control cell movements, tightly linking cellular and genetic patterning. Cell dispersal might be important for the correct positioning of cells and tissues involved in intercellular signaling. The emergence of cell dispersal at the onset of vertebrate evolution indicates a shift from early, lineage-based cellular patterning in small embryos to late, movement-based cellular patterning of polyclones in large embryos. The conservation of the same basic body plan by invertebrate and vertebrate chordates suggests that evolution of the embryonic period preceding the phylotypic stage was by intercalary co-option of basic cell activities present in the ancestral metazoan cell.

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