Quantitative trait loci on chromosomes 9 and 19 modulate AII amacrine cell number in the mouse retina.

Sequence variants modulating gene function or expression affect various heritable traits, including the number of neurons within a population. The present study employed a forward-genetic approach to identify candidate causal genes and their sequence variants controlling the number of one type of retinal neuron, the AII amacrine cell. Data from twenty-six recombinant inbred (RI) strains of mice derived from the parental C57BL/6J (B6/J) and A/J laboratory strains were used to identify genomic loci regulating cell number.

A Developmental Analysis of Juxtavascular Microglia Dynamics and Interactions with the Vasculature.

Microglia, a resident CNS macrophage, are dynamic cells, constantly extending and retracting their processes as they contact and functionally regulate neurons and other glial cells. There is far less known about microglia-vascular interactions, particularly under healthy steady-state conditions. Here, we use the male and female mouse cerebral cortex to show that a higher percentage of microglia associate with the vasculature during the first week of postnatal development compared with older ages and that the timing of these associations is dependent on the fractalkine receptor (CX3CR1).

Complement Targets Newborn Retinal Ganglion Cells for Phagocytic Elimination by Microglia.

Microglia play important roles in shaping the developing CNS, and at early stages they have been proposed to regulate progenitor proliferation, differentiation, and neuronal survival. However, these studies reveal contradictory outcomes, highlighting the complexity of these cell-cell interactions. Here, we investigate microglia function during embryonic mouse retina development, where only microglia, progenitors, and neurons are present.

Modulates Bipolar Cell Number in the Mouse Retina.

The present study interrogated a quantitative trait locus (QTL) on Chr 4 associated with the population sizes of two types of bipolar cell in the mouse retina. This locus was identified by quantifying the number of rod bipolar cells and Type 2 cone bipolar cells across a panel of recombinant inbred (RI) strains of mice derived from two inbred laboratory strains, C57BL/6J (B6/J) and A/J, and mapping a proportion of that variation in cell number, for each cell type, to this shared locus. There, we identified the candidate gene ().

Genetic Control of Rod Bipolar Cell Number in the Mouse Retina.

Genetic variants modulate the numbers of various retinal cell types in mice. For instance, there is minimal variation in the number of rod bipolar cells (RBCs) in two inbred strains of mice (A/J and C57BL/6J), yet their F1 offspring contain significantly more RBCs than either parental strain. To investigate the genetic source of this variation, we mapped the variation in the number of RBCs across 24 genetically distinct recombinant inbred (RI) strains (the AXB/BXA strain-set), seeking to identify quantitative trait loci (QTL).

Sox2 regulates astrocytic and vascular development in the retina.

Sox2 is a transcriptional regulator that is highly expressed in retinal astrocytes, yet its function in these cells has not previously been examined. To understand its role, we conditionally deleted Sox2 from the population of astrocytes and examined the consequences on retinal development. We found that Sox2 deletion does not alter the migration of astrocytes, but it impairs their maturation, evidenced by the delayed upregulation of glial fibrillary acidic protein (GFAP) across the retina.

Alternative splicing of the LIM-homeodomain transcription factor Isl1 in the mouse retina.

Islet-1 (Isl1) is a LIM-homeodomain (LIM-HD) transcription factor that functions in a combinatorial manner with other LIM-HD proteins to direct the differentiation of distinct cell types within the central nervous system and many other tissues. A study of pancreatic cell lines showed that Isl1 is alternatively spliced generating a second isoform, Isl1β, which is missing 23 amino acids within the C-terminal region. This study examines the expression of the canonical and alternative Isl1 transcripts across other tissues, in particular, within the retina, where Isl1 is required for the differentiation of multiple neuronal cell types.

Sox2 regulates cholinergic amacrine cell positioning and dendritic stratification in the retina.

The retina contains two populations of cholinergic amacrine cells, one positioned in the ganglion cell layer (GCL) and the other in the inner nuclear layer (INL), that together comprise ∼1/2 of a percent of all retinal neurons. The present study examined the genetic control of cholinergic amacrine cell number and distribution between these two layers. The total number of cholinergic amacrine cells was quantified in the C57BL/6J and A/J inbred mouse strains, and in 25 recombinant inbred strains derived from them, and variations in their number and ratio (GCL/INL) across these strains were mapped to genomic loci.

Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations.

Medulloblastomas are the most common malignant brain tumours in children. Identifying and understanding the genetic events that drive these tumours is critical for the development of more effective diagnostic, prognostic and therapeutic strategies. Recently, our group and others described distinct molecular subtypes of medulloblastoma on the basis of transcriptional and copy number profiles.

Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner.

Microglia are the resident CNS immune cells and active surveyors of the extracellular environment. While past work has focused on the role of these cells during disease, recent imaging studies reveal dynamic interactions between microglia and synaptic elements in the healthy brain. Despite these intriguing observations, the precise function of microglia at remodeling synapses and the mechanisms that underlie microglia-synapse interactions remain elusive.