Cell Tissue Res DOI 10.1007/s00441-014-1979-5
REVIEW
Progenitor genealogy in the developing cerebral cortex Sophie Laguesse & Elise Peyre & Laurent Nguyen
Received: 26 March 2014 / Accepted: 28 July 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract The mammalian cerebral cortex is characterized by a complex histological organization that reflects the spatiotemporal stratifications of related stem and neural progenitor cells, which are responsible for the generation of distinct glial and neuronal subtypes during development. Some work has been done to shed light on the existing filiations between these progenitors as well as their respective contribution to cortical neurogenesis. The aim of the present review is to summarize the current views of progenitor hierarchy and relationship in the developing cortex and to further discuss future research directions that would help us to understand the molecular and cellular regulating mechanisms involved in cerebral corticogenesis. Keywords Cortex . Progenitor . Division . Neuron . Cell fate
Introduction During mammalian development, the cerebral cortex arises from the dorsal telencephalon. Corticogenesis is a highly dynamic process that requires the generation of different classes of neurons that are later distributed within layers regionally organized into sensory, motor and association areas (Rash and Grove 2006). As progenitors give birth to successive S. Laguesse : E. Peyre : L. Nguyen (*) GIGA-Neurosciences, University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium e-mail: [email protected] S. Laguesse : E. Peyre : L. Nguyen Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium L. Nguyen Walloon Excellence in Lifesciences and Biotechnology (WELBIO), University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium
waves of pyramidal projection neurons, cortical layering develops in an inside–out manner, where later-born neurons migrate to the most superficial layers (Gupta et al. 2002). Projection neurons migrate radially to settle in their appropriate cortical layer and grow axonal projections towards cortical or sub-cortical targets. GABAergic interneurons are born in the ventral forebrain (Anderson et al. 1997) and migrate from the ganglionic eminences along multiple tangential paths to integrate local cortical networks. The development of the cortex requires a continuous rearrangement of a primordial structure that progresses through successive steps including proliferation, specification, migration, and neuronal differentiation. Disrupting the completion of one or several of these events can lead to brain malformations such as microcephaly or lissencephaly. In this review, we will establish the genealogy of the different types of progenitors that generate projection neurons during corticogenesis. In addition, we will also address the mechanisms that control the balance between progenitor selfrenewal and neuron generation.
Cortical progenitors During corticogenesis, the progenitors of projection neurons are distinguished by specific features including cellular morphology, mitotic division behavior, expression of specific combination of molecular markers, and daughter cell fate acquisition (Gotz and Huttner 2005; Miyata et al. 2004; Noctor et al. 2004). In addition, cortical progenitors are classified into two groups according to the location of their mitosis in the developing cortical wall. In the developing cortex, apical progenitors (APs) divide above the ventricular surface; they comprise neuroepithelial cells (NEs), radial glial cells (RGs) and short neural precursors (SNPs). The basal progenitors (BPs) divide abventricularly either in the upper part of the
Cell Tissue Res
At early stages of development, the neural plate is composed of a pseudostratified epithelium of neuroepithelial cells (NEs) that aligns above the future lateral ventricle. These cells represent the basis of the cortical genealogy tree, as they will give rise directly or indirectly to all neuronal and glial cells that compose the adult cerebral cortex (Gotz and Huttner 2005; Noctor et al. 2001). The pseudostratification of the neuroepithelium arises from the interkinetic nuclear migration of NEs (discussed later). NEs are highly polarized along their apico-basal axis and are attached to both ventricular and pial surfaces (Fig. 1). The small apical domain of these cells is separated from the basolateral domain by tight junctions that are present at the most apical end of the lateral plasma membrane, preventing lateral diffusion of apical proteins
(Weigmann et al. 1997; Zhadanov et al. 1999). NEs are also coupled via gap junctions, which are located at the apical process. These gap junctions allow the direct intercellular transfer of ions and small molecules, required for important neuronal processes such as calcium wave propagations (Elias and Kriegstein 2008). The apical membrane is also characterized by a protrusion that extends into the lateral ventricle (Louvi and Grove 2011). This structure is the primary cilium, which functions as a cellular antenna to detect signals present in the cerebrospinal fluid (Lehtinen et al. 2011). The primary cilium grows from the basal body, a modified centriole located at the cytoplasmic membrane. It is present during interphase and is disassembled prior to entry into mitosis, so centrioles can function to organize the poles of the mitotic spindle (Garcia-Gonzalo and Reiter 2012; Kim and Dynlacht 2013; Seeley and Nachury 2010). Before the onset of neurogenesis, NEs undergo a phase of expansion thanks to symmetric divisions, giving rise to two identical progenitors and thereby increasing their number (Rakic 1995; Fig. 1). NEs switch to asymmetric divisions at the onset of neurogenesis to allow neuron generation and selfrenewal (Gotz and Huttner 2005). As cortical development proceeds, NEs undergo changes in their gene expression
Fig. 1 Neural progenitor cells classified according to their location at Mphase. Apical progenitors (APs) define neuroepithelial cells (NEs), short neural precursors (SNPs) and radial glial cells (RGs). NEs form the neural tube epithelium (
REVIEW
Progenitor genealogy in the developing cerebral cortex Sophie Laguesse & Elise Peyre & Laurent Nguyen
Received: 26 March 2014 / Accepted: 28 July 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract The mammalian cerebral cortex is characterized by a complex histological organization that reflects the spatiotemporal stratifications of related stem and neural progenitor cells, which are responsible for the generation of distinct glial and neuronal subtypes during development. Some work has been done to shed light on the existing filiations between these progenitors as well as their respective contribution to cortical neurogenesis. The aim of the present review is to summarize the current views of progenitor hierarchy and relationship in the developing cortex and to further discuss future research directions that would help us to understand the molecular and cellular regulating mechanisms involved in cerebral corticogenesis. Keywords Cortex . Progenitor . Division . Neuron . Cell fate
Introduction During mammalian development, the cerebral cortex arises from the dorsal telencephalon. Corticogenesis is a highly dynamic process that requires the generation of different classes of neurons that are later distributed within layers regionally organized into sensory, motor and association areas (Rash and Grove 2006). As progenitors give birth to successive S. Laguesse : E. Peyre : L. Nguyen (*) GIGA-Neurosciences, University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium e-mail: [email protected] S. Laguesse : E. Peyre : L. Nguyen Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium L. Nguyen Walloon Excellence in Lifesciences and Biotechnology (WELBIO), University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium
waves of pyramidal projection neurons, cortical layering develops in an inside–out manner, where later-born neurons migrate to the most superficial layers (Gupta et al. 2002). Projection neurons migrate radially to settle in their appropriate cortical layer and grow axonal projections towards cortical or sub-cortical targets. GABAergic interneurons are born in the ventral forebrain (Anderson et al. 1997) and migrate from the ganglionic eminences along multiple tangential paths to integrate local cortical networks. The development of the cortex requires a continuous rearrangement of a primordial structure that progresses through successive steps including proliferation, specification, migration, and neuronal differentiation. Disrupting the completion of one or several of these events can lead to brain malformations such as microcephaly or lissencephaly. In this review, we will establish the genealogy of the different types of progenitors that generate projection neurons during corticogenesis. In addition, we will also address the mechanisms that control the balance between progenitor selfrenewal and neuron generation.
Cortical progenitors During corticogenesis, the progenitors of projection neurons are distinguished by specific features including cellular morphology, mitotic division behavior, expression of specific combination of molecular markers, and daughter cell fate acquisition (Gotz and Huttner 2005; Miyata et al. 2004; Noctor et al. 2004). In addition, cortical progenitors are classified into two groups according to the location of their mitosis in the developing cortical wall. In the developing cortex, apical progenitors (APs) divide above the ventricular surface; they comprise neuroepithelial cells (NEs), radial glial cells (RGs) and short neural precursors (SNPs). The basal progenitors (BPs) divide abventricularly either in the upper part of the
Cell Tissue Res
At early stages of development, the neural plate is composed of a pseudostratified epithelium of neuroepithelial cells (NEs) that aligns above the future lateral ventricle. These cells represent the basis of the cortical genealogy tree, as they will give rise directly or indirectly to all neuronal and glial cells that compose the adult cerebral cortex (Gotz and Huttner 2005; Noctor et al. 2001). The pseudostratification of the neuroepithelium arises from the interkinetic nuclear migration of NEs (discussed later). NEs are highly polarized along their apico-basal axis and are attached to both ventricular and pial surfaces (Fig. 1). The small apical domain of these cells is separated from the basolateral domain by tight junctions that are present at the most apical end of the lateral plasma membrane, preventing lateral diffusion of apical proteins
(Weigmann et al. 1997; Zhadanov et al. 1999). NEs are also coupled via gap junctions, which are located at the apical process. These gap junctions allow the direct intercellular transfer of ions and small molecules, required for important neuronal processes such as calcium wave propagations (Elias and Kriegstein 2008). The apical membrane is also characterized by a protrusion that extends into the lateral ventricle (Louvi and Grove 2011). This structure is the primary cilium, which functions as a cellular antenna to detect signals present in the cerebrospinal fluid (Lehtinen et al. 2011). The primary cilium grows from the basal body, a modified centriole located at the cytoplasmic membrane. It is present during interphase and is disassembled prior to entry into mitosis, so centrioles can function to organize the poles of the mitotic spindle (Garcia-Gonzalo and Reiter 2012; Kim and Dynlacht 2013; Seeley and Nachury 2010). Before the onset of neurogenesis, NEs undergo a phase of expansion thanks to symmetric divisions, giving rise to two identical progenitors and thereby increasing their number (Rakic 1995; Fig. 1). NEs switch to asymmetric divisions at the onset of neurogenesis to allow neuron generation and selfrenewal (Gotz and Huttner 2005). As cortical development proceeds, NEs undergo changes in their gene expression
Fig. 1 Neural progenitor cells classified according to their location at Mphase. Apical progenitors (APs) define neuroepithelial cells (NEs), short neural precursors (SNPs) and radial glial cells (RGs). NEs form the neural tube epithelium (
