Adult Upper Cortical Layer Specific Transcription Factor CUX2 Is Expressed in Transient Subplate and Marginal Zone Neurons of the Developing Human Brain

Cut-Like Homeobox 2 (Cux2) is a transcription factor involved in dendrite and spine development, and synapse formation of projection neurons placed in mouse upper neocortical layers. Therefore, Cux2 is often used as an upper layer marker in the mouse brain. However, expression of its orthologue CUX2 remains unexplored in the human fetal neocortex. Here, we show that CUX2 protein is expressed in transient compartments of developing neocortical anlage during the main fetal phases of neocortical laminar development in human brain. During the early fetal phase when neurons of the upper cortical layers are still radially migrating to reach their final place in the cortical anlage, CUX2 was expressed in the marginal zone (MZ), deep cortical plate, and pre-subplate. During midgestation, CUX2 was still expressed in the migrating upper cortical neurons as well as in the subplate (SP) and MZ neurons. At the term age, CUX2 was expressed in the gyral white matter along with its expected expression in the upper layer neurons. In sum, CUX2 was expressed in migratory neurons of prospective superficial layers and in the diverse subpopulation of transient postmigratory SP and MZ neurons. Therefore, our findings indicate that CUX2 is a novel marker of distinct transient, but critical histogenetic events during corticogenesis. Given the Cux2 functions reported in animal models, our data further suggest that the expression of CUX2 in postmigratory SP and MZ neurons is associated with their unique dendritic and synaptogenesis characteristics.

Postembryonic screen for mutations affecting spine development in zebrafish

The spinal vertebral column gives structural support for the adult body plan, protects the spinal cord, and provides muscle attachment and stability, which allows the animal to move within its environment. The development and maturation of the spine and its physiology involve the integration of multiple musculoskeletal tissues including bone, cartilage, and fibrocartilaginous joints, as well as innervation and control by the nervous system. One of the most common disorders of the spine in human is adolescent idiopathic scoliosis (AIS), which is characterized by the onset of an abnormal lateral curvature of the spine of <10° around adolescence, in otherwise healthy children. The genetic basis of AIS is largely unknown. Systematic genome-wide mutagenesis screens for embryonic phenotypes in zebrafish have been instrumental in the understanding of early patterning of embryonic tissues necessary to build and pattern the embryonic spine. However, the mechanisms required for postembryonic maturation and homeostasis of the spine remain poorly understood. Here we report the results from a small-scale forward genetic screen for adult-viable recessive and dominant mutant zebrafish, displaying overt morphological abnormalities of the adult spine. Germline mutations induced with N-ethyl N-nitrosourea (ENU) were transmitted and screened for dominant phenotypes in 1,229 F1 animals, and subsequently bred to homozygosity in F3 families, from these, 314 haploid genomes were screened for recessive phenotypes. We cumulatively found 39 adult-viable (3 dominant and 36 recessive) mutations each leading to a defect in the morphogenesis of the spine. The largest phenotypic group displayed larval onset axial curvatures, leading to whole-body scoliosis without vertebral dysplasia in adult fish. Pairwise complementation testing within this phenotypic group revealed at least 16 independent mutant loci. Using massively-parallel whole genome or whole exome sequencing and meiotic mapping we defined the molecular identity of several loci for larval onset whole-body scoliosis in zebrafish. We identified a new mutation in the skolios/kinesin family member 6 (kif6) gene, causing neurodevelopmental and ependymal cilia defects in mouse and zebrafish. We also report several recessive alleles of the scospondin and a disintegrin and metalloproteinase with thrombospondin motifs 9 (adamts9) genes, which all display defects in spine morphogenesis. Many of the alleles characterized thus far are non-synonymous mutations in known essential scospondin and adamts9 genes. Our results provide evidence of monogenic traits that are critical for normal spine development in zebrafish, that may help to establish new candidate risk loci for spine disorders in humans.

Transcriptome analysis reveals the genetic basis underlying the development of skin appendages and immunity in hedgehog(Atelerix albiventris)

Background: The expression of hair features is an evolutionary adaptation resulting from interactions between many organisms and their environment. Elucidation of the mechanisms that underlie the expression of such traits is a topic in evolutionary biology research; however, the genetic basis of skin appendage development and differentiation remains poorly understood. Therefore, we assessed the de novo transcriptome of the hedgehog ( Atelerix albiventris ) at three developmental stages and compared gene expression profiles between abdomen hair and dorsal spine tissues. Results: We identified 328,576 unigenes in our transcriptome, among which 3,598 were differentially expressed between hair- and spine-type tissues. We identified 3 keratin genes related to hair and spine development through comparative analysis of tissues before and after growth of skin appendages. Dorsal and abdomen skin tissues 5 days after birth were compared and the resulting differentially expressed genes (DEGs) were mainly enriched in keratin filament, intermediate filament, epithelium cell differentiation, and epidermis development based on GO enrichment analysis, and tight junction, p53, and cell cycle signaling pathways based on KEGG enrichment analysis. Expression variations of MBP8, SFN, Wnt10, KRT1 , and KRT2 may be the main factors regulating hair and spine differentiation for the hedgehog. Strikingly, DEGs in hair-type tissues were also significantly enriched in immune-related terms and pathways with hair-type tissues exhibiting more upregulated immune genes than spine-type tissues. Thus, we propose that spine development was an adaptation that provided protection against injuries or stress and reduced hedgehog vulnerability to infection. Conclusion: Our study provided a list of potential genes involved in the regulation of skin appendage development and differentiation in A. albiventris . This is the first transcriptome survey of hair traits for a non-model mammal species, and the candidate genes provided here may provide valuable information for further studies of skin appendages and skin disorder treatments.